Lecture 2: DNA, Central Dogma, Organization of Genes and Chromosomes ____________________________________________________________________________ Genes, Chromatin, and Chromosomes: - - - - - Central Dogma of Microbiology: - Coined by Francis Crick (co-founder of the structure of DNA). - “ The central dogma of molecular biology deals with the detailed residue-byresidue transfer of sequential information. It states that such information cannot be transferred from protein to either protein or nucleic acid.” ~Francis Crick, 1970. - Concerns the residue by residue transfer of sequential information. - Involves molecules transferring in a sequential manner. - Information cannot be transferred: - From protein to protein. - From protein to nucleic acid. Summarized Pathway: - a. DNA is transcribed into RNA. - b. RNA is translated into protein. - c. RNA can be reverse transcribed into DNA in certain situations. - d. DNA replicates itself. Notes on Central Dogma: - RNA in some instances can be reverse transcribed into DNA. - Examples: - i. In molecular techniques like quantitative PCR. - ii. Certain organisms or viruses during their regular life history. Basic Cell Structure: Cell contains cell membrane. - The watery interior of cells is surrounded by the plasma membrane, a two layered shell of phospholipids Transmembrane proteins allow molecules to move in and out. Cell membrane: - Composed of a phospholipid bilayer. - Hydrophobic inside, hydrophilic outside. Contains cholesterol molecules to aid in fluidity. Associated with water molecules. - Cell membranes are made of bilayers of phospholipids, each oriented with its hydrophilic “water-loving” head toward a membrane surface and its hydrophobic “water-hating” tail toward the membrane interior. - Cholesterol and proteins are embedded in the membrane structure - Cell Membrane and Interactions: - Molecules interact with the cell membrane. - Various compartments or organelles within the cell membrane. - Structure of the Nucleus: - Nucleus is bounded by inner and outer membranes containing nuclear pore complexes through which materials move into and out of the nucleus. - Nuclear outer membrane is connected to the endoplasmic reticulum. - Endoplasmic reticulum may be studded with ribosomes synthesizing membrane and secreted proteins. - Nucleolus is the site of ribosomal RNA production and assembly of ribosome components. - Nucleolus and nucleus house the genome and various interacting molecules. Genome (DNA) is transcribed into RNA molecules. RNA molecules are transported outside the nucleus. Translation begins as ribosomes associate with RNA molecules. - Other Cellular Structures: - Endoplasmic Reticulum (ER): - Vital for post-translational modifications to proteins. - Involved in signaling proteins to bind other molecules, assisting in transport throughout the cell and even outside it. - Cytosol: - The fluid within the cell. - Contains freely floating ribosomes. - Ribosomes conduct translation as messenger RNAs exit the nuclear pore complex. - Chromatin Fibers: - Found throughout the cell. - Their configuration depends on cell state, division, and cycle. - May be tightly packed or loose, influencing gene expression. - Other Organelles: - Various other organelles and complexes are present. - Electron micrographs provide more detailed visualization. - Context and Overview - Understanding these structures and compartments is essential for navigating and comprehending the significance of these complexes in future discussions. - Fundamental knowledge that should already be known or learned for a clearer bird's-eye view. - Chromatin: - Freely floating within the cell. - State and organization depend on the cell cycle phase. - Can be compact or decondensed. - Cell Cycle Phases and Chromatin: - Essential to consider for understanding molecular interactions within the cell. - Molecules are associated with organelles, macromolecules, and micromolecules dynamically influencing construction, destruction, and functioning. - Chromosomes: - Images and renditions offer insights into appearance and organization. - Includes numerous chromosomes, including sex chromosomes X and Y. - Individual chromosomes visible during cell division. - Highly compacted during M phase of mitosis for easy movement and organization. - Four Major Phases of the Cell Cycle: - G1 Phase: - Unreplicated chromosomal DNA. - Cell constituents are made - Increase in cell size - Synthesis of RNA, lipids and proteins - Cellular components, excluding chromosomes, are duplicated - S Phase: - DNA Replication occurs - G2 Phase: - Preparation for mitosis - Further RNA, lipid, and protein synthesis - DNA repair occurs - M Phase: - Chromosome segregation - Chromatin condenses. - Chromosomes become more organized and visible. - Chromosomes appear in typical, stereotypical organization. - Chromatin organization is largely dictated by the cell's cycle state. - Cell division into two daughter cells - Additional Cell Cycle Phase: - G0 phase: - Cells are temporarily or permanently out of the cell cycle and stop cycling - Not typically considered among the four major phases Transition to DNA: - Photo 51 by Rosalind Franklin played a crucial role in elucidating the DNA structure. - DNA Structure: - Composed of two complementary strands wound around each other to form a double helix. - Unwinding of the double helix is necessary for processes like DNA replication. - DNA Replication: - Unwound strands (illustrated in blue) serve as templates. - Daughter strands (shown in gray) built during the DNA replication process. - Facilitated by DNA polymerase and other proteins and molecules. - One double helix is converted into two double helices. - The two strands unwind and serve as templates for synthesis of complementary strands to yield two identical copies of the original strand. - Genetic information is encoded in the linear order of bases. - Bases in DNA: - Different colors within the DNA double helix represent various bases: A, G, T, C. - Two main categories of bases: - Purines: A and G. - Pyrimidines: C, T, and U (in the context of RNA). - Stabilization and Bonding: - The double helix is stabilized by hydrogen bonds. - Hydrogen bonds form between different bases in specific sequences or complementation. - Base pairing: - A with T (or U in RNA) - G with C. - The process of complementation and base pairing elucidated by Ernst Chargaff was crucial for understanding DNA structure. Key Features of Nucleotides: - 3 Key Features: - Bases: - Bases include Adenine (A), Guanine (G), Cytosine (C), Thymine (T) (only in DNA), and Uracil (U) (only in RNA). - A, G, and C are found in both DNA and RNA. - Purines (A and G) and Pyrimidines (C, T, and U) are grouped based on structural similarities. - Pentose Sugar: - Comes in two forms: ribose and deoxyribose. - Deoxyribose is a component of DNA, ribose is a component of RNA. - Phosphate Group: - Forms the backbone of the DNA/RNA structure. - Linked through phosphodiester bonds. - DNA Structure: - Backbone composed of alternating phosphate and pentose sugar - Inner part of the helic formed by hydrogen bonds between complementary bases - Structure can be illustrated in various ways including stick diagrams and 3D models - Major and Minor Grooves: - DNA’s 3D structure includes major and minor grooves - Sites where proteins and other macromolecules can interact with the DNA - In 1953, James D. Watson and Francis H. C. Crick proposed DNA double helical structure, based on the analysis of DNA fiber xray diffraction patterns generated by Rosalind Franklin and Maurice Wilkins and ErwinChargaff’s revelation that the percentages of A=T and G=C. - - - - A) Space Filling Model of DNA: - Bases (light shades) project inward from the sugar-phosphate backbones (dark red and blue) of each strand. - The major and minor grooves are lined by potential hydrogen bond donors and acceptors (yellow), which can interact with proteins and other molecules B) Chemical structure of DNA double helix shows two sugar-phosphate backbones and two hydrogen bonds in A-T and three hydrogen bonds in G-C base pairs. Base Pairing Patterns: - A will pair with T or U in RNA always forming two bonds - C will pair with G always forming three bonds - Critical for understanding the potential combinations and interactions in the DNA structure Interactions with Proteins: - Proteins (e.g. transcription and replication factors) can interact with - DNA in the grooves to regulate replication or transcription Example: - TATA Box Binding Protein (TBP) can bend DNA to enable various cellular processes - Bonding in DNA: - Adeninine (A) forms 2 bonds with Thymine (T) - Cytosine (C) forms 3 bonds with Guanine (G) - 3>2 - Influence on Energy Required for Unwinding DNA: - Amount and type of bonds influence energy or activity needed to unwind DNA - More energy needed to break G-C bonds (hydrogen bonds) compared to A-T bonds - Context: DNA replication and PCR - Going from double to single stranded DNA important in replication and PCR - Separating DNA strands necessary for artificial replication in PCR - GC content influences temperature needed to break bonds and separate strands - Temperature of melting (Tm): - Defined as the temperature where half the double stranded DNA bases have melted or denatured - Higher GC content increases the Tm - More energy required to denature DNA with higher GC content - Effect of GC content on denaturation: - Increase in GC content increases the temperature required for denatureation - The greater the G+C percentage, the higher the Tm - Relationship not always linear - Influenced by various factors including presence of salts, enzymes, and other molecules Chemical and physical environment of DNA also plays a role Additional factors influencing denaturation: - Enzymes and other molecules can catalyze denaturation - Influence the energy required for the processes - Can make denaturation faster, slower, easier, or harder - Reversible denaturation and renaturation of DNA is the basis for nucleic acid hybridization, which is key to powerful molecular techniques including PCR Gene Structure Overview: - Gene structure– control regions, exons, and introns - Genes have specific structures that include control regions - Control regions influence gene activity - Exons and introns: - Exons: coding regions of DNA - Introns: non coding regions of DNA - Both are part of the gene’s structure - Gene products: - Genes encode for single proteins or different isoforms - Process is influenced by the gene’s structure and control regions - Gene families: - Groups of related genes that have similarities in their sequences and functions - Arise from gene duplication or different forms of recombination - Gene families arise from gene duplication during unequal meiosis recombination - Functional RNAs: - Many genes encode functional RNAs - Not translated into proteins but carry out structural or enzymatic functions - Variety in gene encoding: - Genes can encode proteins, RNA molecules, and other structures - Different types of RNA molecules have various functions - Many genes encode functional RNAs that are not translated into proteins but perform significant functions, such as rRNAs, tRNAs, and miRNAs Genes and Chromosomes: - Nucleus & chromosome location: - The nucleus houses DNA and chromosomes - Chromosomes have a specific structural organization within the nucleus - Structure breakdown: - Double stranded DNA: - Basic form of genetic material - Discussed in previous sections - Nucleosome complexes: - Double stranded DNA woven around these structures - Appear like beads on a strand - Made up of histone molecules - Chromatin fibers: - Nucleosomes come together and condense to form these fibers - Size range from 5 to 24 nanometers - Topological Association Domains (TAD): - Chromatin fibers form these 3D domains as they condense further - Important for DNA folding and organization within the nucleus - Compacted chromosomes: - TAD’s further compact into chromosomes - These chromosomes can be in densely compacted forms or more loosely packed forms - Regional specificity in nucleus: - Chromosomes maintain specific locations within the nucleus, ensuring organization - This regionalization can change based on the regulation of chromosomes - - Single human cell DNA measures about 2 meters in total length and is contained within nuclei with diameters of less than 10 μm — a compaction ratio of greater than 10^5 to 1 Each chromosome consists of a single DNA molecule (as long as 280 Mb in humans), organized into increasing levels of condensation from nucleosomes to higher order chromatin folding by histone and nonhistone proteins. - In the sentence, Mb stands for "megabase" or "megabase pairs," a unit used in genomics and molecular biology to describe the length of DNA. One megabase (Mb) is equal to one million base pairs. It is a measure of the number of base pairs in a DNA sequence and is used to estimate the size of a gene, chromosome, or genome. - Any given portion of highly compacted DNA can be accessed for transcription, replication, and repair of damage without the long DNA molecules becoming tangled or broken Exon and Gene Duplication: - Gene Families: - Genes that are present in the form of gene families. - Gene families consist of many different genes that are very similar to each other. - As a whole, these genes are distinct when viewed together. - Protein Families: - The genes within gene families encode proteins that are a part of corresponding protein families. - Origins of Gene and Protein Families: - Recombination Events - Can lead to a chromosome acquiring multiple copies of an exon. - Example: - A recombination event might result in a recombinant chromosome with exons 1, 2, 3, and another 3. Meanwhile, the other chromosome may only have exons 1 and 2. - This duplication of exons can happen during recombination. - Gene Duplication: - Entire genes can be swapped between parental chromosomes during recombination. - Result: - One chromosome might end up with two copies of the same gene, while the other chromosome might not have that gene at all. - For instance, one chromosome might have 2 Beta globin genes, while the other has none. - Exon and Gene Duplication: - These are simplistic descriptions, but both exon and gene duplication can occur during recombination. - Recombination can produce multiple copies of a given gene or exon within a gene. - This process is crucial for the evolution and diversification of gene families. Simple and Complex Eukaryotic Transcription Units: - (a) Simple transcription unit (~10 percent of human transcripts): - A monocistronic region extending from the 5ʹ cap site to the 3ʹ poly(A) site with introns removed that encodes one protein. - Mutations in a transcription-control region (a or b) may reduce or prevent transcription, thus reducing or eliminating synthesis of the encoded protein. - A mutation within an exon (c) may result in an abnormal protein with diminished activity. - A mutation within an intron (d) that introduces a new splice site results in an abnormally spliced mRNA encoding a mutated protein - Gene Overview: - A gene is a fundamental unit of heredity and a sequence of nucleotides in DNA. - Control regions help regulate and orchestrate the activity of genes. - Gene Structure: Basic Distinction - Simple Gene Structure: - About 10% of our genome. - Major components: - Control Regions: Dark blue squares upstream of exons. - Upstream refers to regions before exons. - Cap Site: Detail discussed later. - - Exons: Elements that contribute to amino acids following transcription and translation. Introns: Elements between exons that do not encode protein (not translated). Transcription: - Transcribed into an RNA molecule called messenger RNA (mRNA). - Exons in RNA form are spliced together during RNA processing. - Mature mRNA transcript transported out of the nucleus and translated into protein sequence. - - Mutations in Simple Gene Structure: - In Exon: May result in an abnormal protein with diminished activity. - In Intron: Can influence the splicing properties and impact isoforms after splicing. - In Control Regions: Can prevent, bias, or perturb transcription activity. - Enzymes associate with control regions to influence the rate of transcription. - Mutations can influence the levels of production of that gene. Complex Gene Structure: - The rest of the genome. - More intricate compared to simple gene structure. - Consequences of Mutations: - Exon: - May lead to the production of an abnormal protein, potentially affecting the protein’s function. - Encodes amino acids of the eventual protein. - Intron: - May influence the splicing properties of the gene structure. - Can lead to abnormal splicing or RNA processing. - Control Regions: - Mutations can prevent, bias, or perturb transcription. - Affect the activity of the gene by altering the transcription rate. - Influence the levels of gene production. - Impacts: - Changes in nucleotides can impact: - Splicing - Function of the eventual protein Amount of transcription - Majority of genes in our genome are complex. - Alternative Splicing: - Involves the inclusion or exclusion of certain exons during RNA processing. - Exons can either be retained or spliced out, leading to different mRNA transcripts. - Depending on the cellular context, enzymes might interact with intronic regions and exonic boundaries to determine exon inclusion. - Outcome of whether an exon is included/excluded can vary: - Protein could become dysfunctional or truncated. - May remain functional but be more cell-specific. - Can enhance or alter the protein's activity. - May affect the enzyme's active site if the exon affects an enzyme. - Can influence protein localization within the cell. - Different Transcripts from Same Gene: - - mRNA can be processed to have the same 5 and 3 prime exons but different internal exons. Middle example: Two possible transcripts can emerge from a gene: - One with exon 2 and a specific 3' UTR. - Another without exon 2, making exon 3 the second exon and having a different 3' end and poly-A sequence. 3' UTR (Untranslated Region): - Does not contribute to the protein but plays a key role in mRNA regulation. - Contains sequences where different proteins can bind. - Determines mRNA behavior, localization, and stability within the cell. - Different Gene Starts & Control Regions: - A gene can have multiple starting points. - Two distinct 5' caps or start exons illustrated as exon 1A and exon 1B. - The presence of multiple control regions within a gene: - Control region 1 may initiate transcription at one location, while another downstream control region may dictate a different transcription start. - Such diversity in gene structures can lead to: - Different functional or structural properties for the encoded protein. - Multiple transcripts or alternative isoforms emerging from a single gene, depending on cellular context. - RNA Splicing: - During RNA processing: - Introns are removed. - Exons are retained. - Exons can be spliced together in various patterns depending on: - Cell-specific proteins. - Splicing factors that determine the patterns of splicing, known as the "splicing code". - Different cells may have unique combinations of proteins, influencing the exon inclusion/exclusion. - Noted disease example: - Understanding the control of exon retention can be vital in molecular medicine. - One drug developed in the past decade, based on this concept, is saving many children's lives by influencing splicing patterns. - Genome Enrichment in Different Organisms: - Comparison between simple and complex organisms. - Example: genomic region highlighted in green indicating various exons. - Bottom shows more complexity (more exons) compared to the top. - Yeast (Saccharomyces cerevisiae) vs Human Genome: - Yeast chromosome 3 shows numerous exons, appears complex. - Human chromosome 11 contains the beta globin gene cluster with multiple beta globin genes. - Human beta globin genes appear less in number but have a more complex structure. - Beyond Exons – Importance of Non-Coding Regions: - Human globin gene cluster showcases complexity beyond exons. - Non-coding regions, previously deemed as “junk DNA,” hold significant importance. - House regulatory sequences critical for gene activity and regulation. - Different regions allow various transcription factors to bind, leading to diverse activity and regulation. - Non-coding regions impact: - When genes are transcribed. - How much they’re transcribed. - In which cell types they’re transcribed. - Which exons are included in the transcription. - Dynamic Transcription Leads to Varied Biochemical Functions: - Different combinations of dynamic transcription contribute to varied biochemical functionalities. - More can be achieved with less, owing to the dynamic regulatory aspect found in the human genome, compared to a unicellular yeast organism. - More complex genome structure in humans leads to greater variability and adaptability in gene expression and function. - Expanding the Central Dogma: From DNA to Various RNA Molecules Beyond Protein Coding: - The central dogma explains the translation from DNA to RNA to proteins. - However, DNA to RNA encompasses a broad array of molecules, particularly different RNA types. - Diverse RNA Types: - mRNAs (Messenger RNAs): - Connect the DNA world to the protein world. - Templates that the ribosome translates into amino acids. - rRNAs (Ribosomal RNAs): - Human genome encodes for approximately 300 ribosomal RNAs. - Play essential roles in forming the ribosome structure, aiding in translation. - tRNAs (Transfer RNAs): - Crucial for protein synthesis. - Carry and mediate amino acid building blocks in peptide formation. - snRNAs (Small Nuclear RNAs): - Covered in RNA processing lectures. - miRNAs (Micro RNAs): - Covered in epigenetic lectures. - Various Other RNAs: - Many different RNA types beyond current understanding, still under research. - RNA’s Functional Diversity: - Structural Role: - e.g., rRNAs play a significant part in structuring the ribosome. - Enzymatic Activity: - Some RNA molecules conduct enzymatic activities, like in ribozymes in the ribosome. - RNA in Translation: - Play various roles in the translation process. - Other Functions: - Involved in regulating gene expression levels, splicing, and more. Overall: - Cellular function is not confined to the protein world. - Various nucleotide-based molecules, especially diverse RNA types, are pivotal for the structural and functional aspects of cells. - This broader understanding emphasizes the complexity and versatility of RNA molecules in cellular processes beyond mere protein coding, expanding the traditional comprehension of the central dogma. - - Prokaryotic and Lower Eukaryotic Genomes: - Gene Density: - High density of genes. - Non-functional Sequences: - These genomes contain few sequences that do not have a known function. - This dense arrangement means the DNA is primarily used for encoding proteins or functional RNA molecules. - Multicellular Animal and Plant Genomes: - Gene Density: - These genomes have a lower gene density compared to prokaryotic organisms. - Introns: - Non-coding sequences found within genes. - These do not encode for proteins but play roles in gene regulation, splicing, and evolution. - Non-coding Sequences: - Apart from introns, multicellular genomes also contain other sequences that don't code for proteins. - These can have structural, regulatory, or sometimes unknown roles. - Repetitive Sequences: - Tandem Repeats: - Sequences that appear in multiple copies next to each other. - This includes sequences like telomeres and centromeres. - Alu Repeats: - Specific to primates, Alu sequences are a type of short interspersed nuclear element (SINE). - They are the most common repeat in the human genome, found around every 3kb. - Applications and Studies Involving Non-coding DNA: - DNA Fingerprinting: - A method used to distinguish between individuals of the same species using only samples of their DNA. - It doesn't sequence the whole genome but rather looks at specific regions with high variability, often involving repetitive sequences. - Protein-DNA Interactions: - Several proteins interact with DNA, not just for replication and repair, but also for regulating gene expression. - By understanding how different protein molecules can interact with DNA sequences, scientists can gain insights into gene regulation, chromosomal structure, and more. - Chromatin Structure: - Nucleosomes: - Chromatin is composed of DNA wrapped around histone proteins, forming nucleosomes. - This organization compacts the DNA and also plays a role in gene regulation by controlling access to the genetic information. - Histone Modification: - Histone Tails: - The tails of histone proteins can be chemically modified (e.g., acetylation, methylation). - Regulation: - These modifications can alter the structure of the chromatin and subsequently impact gene transcription. - Different modifications can either encourage or inhibit the transcription of genes by making the DNA more or less accessible to the transcription machinery. - Chromosome Territories: - Non-overlapping Territories: - In the interphase nucleus, different chromosomes occupy distinct, non-overlapping territories. - Localization Impact: - The specific localization within the nucleus can impact gene expression and function. - Chromosome Organization: - Variability: - Similar genetic information can be organized differently on chromosomes, impacting gene function and regulation. - Chromosome Painting: - Detecting Defects: - Chromosome painting techniques can reveal chromosomal defects and aberrations, useful in diagnosing genetic disorders and studying cancer. - Evolutionary Relationships: - These techniques can also illuminate evolutionary relationships by highlighting chromosomal similarities and differences among species. - Visualization of the Nucleosome: - The nucleosome, as visualized through advanced X-ray crystallography techniques, is a complex structure with DNA wrapped around histone proteins. 147 Base Pairs of DNA: The structure involves about 147 base pairs of DNA wound around an octamer of histone proteins. - Histone Octamer: - Histone Types: - The octamer core comprises two each of four distinct histone proteins: H2A, H2B, H3, and H4. - Pie-Segment Structure: - If visualized as a pie, each histone type would represent a quarter, combining to form the complete octamer. - Color Coding: - Different histone proteins are often color-coded in structural representations for clear differentiation. - DNA Wrapping: - Around the Octamer: - The DNA wraps around this histone octamer, conforming to the spherical shape of the histone proteins. - Top and Side View: - From the top view, the wrapping DNA creates a distinct pattern, and from the side, the intertwined DNA and histone proteins are clearly visible. - Importance: - Structural Role: - The nucleosome plays a crucial role in compacting DNA into the cell nucleus and organizing it for effective functioning. - Regulatory Role: - The configuration of nucleosomes also impacts the accessibility of the DNA for transcription and other cellular processes. - Nucleosome Composition: - DNA-Protein Complex: - A nucleosome is composed of DNA wrapped around a histone octamer. - Adjacent nucleosomes are connected by linker DNA. - Visual Representation: - This arrangement is often depicted as beads on a string, with the "beads" representing nucleosomes and the "string" representing linker DNA. - Visualization through Electron Micrograph: - Electron Microscopy: - The arrangement of nucleosomes and DNA is visible through high-resolution electron microscopy, revealing the structure and organization of chromatin fibers. - Chromatin States: - Euchromatin: - Represents a loosely packed, accessible state of chromatin. - Genomic regions within euchromatin are generally more transcriptionally active because the relaxed chromatin allows access for transcription factors and other regulatory proteins. - Heterochromatin: - Represents a densely packed, less accessible state of chromatin. - Regions within heterochromatin are generally transcriptionally silent due to the compact structure that restricts access to the DNA. - Impact on Gene Activity: - Accessibility: - The state of chromatin (euchromatin or heterochromatin) significantly impacts the accessibility of the DNA to various proteins, including transcription factors and other regulatory molecules. - Transcriptional Regulation: - Heterochromatic Regions: - In tightly packed heterochromatin, the DNA is inaccessible, generally leading to transcriptional silence in these regions. - Euchromatic Regions: - In loosely packed euchromatin, the DNA is accessible, allowing transcription factors and other proteins to bind to the DNA, promoting gene expression and transcription. - Dynamic Chromatin Configuration: - The chromatin configuration is not static. - Depending on various cellular signals and conditions, regions of chromatin can transition between euchromatin and heterochromatin, thus modulating gene expression dynamically in response to cellular needs and environmental cues. - Definition: - Post-Translational Modifications (PTMs): - After translation, proteins, including histones, undergo chemical changes. These alterations involve the addition of functional groups or other proteins, which can significantly impact protein function. - Histone Modifications: - Histone Tails: - Histones possess tails that protrude from the nucleosome. - These tails contain specific amino acid sequences, not arbitrary, primed for modifications. - Types of Modifications: - Methylation (addition of a methyl group) - Acetylation (addition of an acetyl group) - Ubiquitination - Phosphorylation - Implication: - Modifications alter chromatin behavior and genome activity, even though they might appear minor from a chemical perspective. - Effect on Chromatin and Genome Activity: - Altered Chromatin Behavior: - Modifications, particularly on histone tails, impact how chromatin behaves, affecting its structure and accessibility. - Genome Activity: - These changes influence genome activity, including gene transcription levels and other chromosomal activities. - Examples: - Histone Tails Amino Acids: - Histone tails contain amino acids like serines, lysines, and arginines, which can be modified, affecting gene activity and chromatin structure. - Broader Implications: - Beyond Histones: - PTMs are not exclusive to histones and occur in various cellular proteins, diversifying and regulating their functions. - Diverse Modifications: - Amino acids within protein structures, including histone tails, can be subject to multiple modifications, broadening the functional spectrum of proteins. - In Context of Epigenetics and Transcription: - Epigenetic Context: - Histone modifications play a crucial role in epigenetic regulation, affecting gene expression without altering the underlying DNA sequence. - Transcription Context: - Changes in histone tail modifications can influence the transcriptional state of associated genes, impacting gene expression levels. - Overall: - Histone modifications, a subtype of post-translational modifications, offer a layer of regulatory control over gene expression and chromatin dynamics. - These subtle chemical changes on histone tails contribute to the functional diversity of proteins and play a crucial role in the intricate regulation of gene activity and chromosomal functions.
