CHAPTER 19 -- EUKARYOTIC GENE EXPRESSION
YOU MUST KNOW:
 The impact of DNA methylation and histone acetylation on gene expression
 The role of oncogenes, proto-oncogenes, and tumor suppressor genes in cancer.
 The various stages of the protein making process where genes or their products can be turned
on or off.
 That gene regulation can result in cell specialization
Review structure, number and formation of chromosomes
I. Eukaryotic Gene Expression Can Be Regulated at Any Stage
 Organisms have identical genome in almost every cell. However, only about 20 % (or less) of the
genes are active in any given cell.
 Cells must turn genes on or off all the time as a response to internal and external stimuli.
 Regulation of gene expression is also important part of cell specialization -- the modification of
cells to perform specific functions (nerve cell, white blood cell etc.)
 Differential gene expression -- the expression of different genes by cells with the same genome.
 To properly express genes, transcription factors must locate the proper promoter region and
transcribe the correct gene to make a polypeptide at any given time.
 The following picture summarizes all potential control points where the genes or their products
can be turned on or off:

The following are the various stages of gene regulation:
A. Regulation of Chromatin Structure:
 Heterochromatin -- tightly packed parts of chromatin that stains dark under the microscope. Genes
here are usually not expressed.
 Euchromatin -- part of the chromatin that is more loose and usually holds actively transcribing genes
 Histone acetylation -- acetyl groups can be attached to histone proteins to prevent the histones to
bind with each other and tightly pack up. As a result, the chromatin remains lose and easily
transcribed.
 Histone methylation -- methyl groups (-CH3) are attached to the histone tails. This promotes the
condensation (close packing) of the chromatin and makes it less active.
 DNA methylation -- enzymes can also methylate certain bases of the DNA molecule. The
methylated sections of DNA are usually not transcribed. This can lead to long-term inactivation or

genomic imprinting -- the inactivation of the mother's or father's genes in diploid cells at the start of
development.
Epigenetic inheritance -- the modification of the chromatin can be inherited although these
modifications do not change the nucleotide sequence of the DNA. These modifications however,
can also be reversed.
B. Regulation of Transcription Initiation:
 In a eukaryotic genes can be turned on or off during the initiation of transcription. The
complete initiation complex (several transcription factors and RNA polymerase II) have to be
assembled on the promoter region of the gene to initiate transcription. If only a few general
transcription factors bind to the TATA box, only a few mRNA molecules will be produced. To
have high efficiency translation performed, several specific transcription factors need to be
attached to the promoter region.
 The enhancer region can also improve the efficiency of transcription if activator proteins bind to
the enhancer region and those make the enhancer region bind to proteins of the transcription
initiation complex. As a result, the transcription can occur faster, more efficiently.

Some specific transcription factors can also function as repressors to inhibit expression of a
particular gene. These repressors can prevent the binding of activators or other transcription
factors to the promoter region.
C. Mechanisms of Post-Transcriptional Regulation:
Transcription alone will not result in gene expression. To have a functional protein, many things need to
take place after the pre-mRNA is made. Any one of the steps of making a functional mRNA or a
functional protein can be shut down or sped up as part of gene regulation. The following are a few
examples of these regulatory processes:
 RNA processing – Alternative RNA splicing is a good example of a way to form different mRNA
molecules.
 mRNA degradation – mRNA has a limited life span to form proteins. Prokaryotic mRNA can be
broken down within minutes after transcription. In eukaryotes, however, mRNA can survive
longer, sometimes for weeks. This degradation of mRNA can be done by enzymes gradually
breaking down the 5’ cap, poly-A tail than the entire segment of mRNA. Small segments of RNA
molecules (microRNA’s or miRNA) can also attach to the mRNA and prevent translation or can
actually break down the mRNA.


Initiation of translation – regulatory proteins can bind to mRNA and prevent it to bind with the
ribosome during the initiation of translation
Protein processing and degradation – To activate proteins, they need to be modified by either
cleavage of certain parts off (pepsinogen to pepsin) or by attaching phosphate groups to the
protein (protein kinase receptors). Regulatory proteins can stop any of these steps and can
make proteins dysfunctional.
II. Cancer Results from Genetic Changes that Affect Cell Cycle Control:
 Review: cancer stages, treatment, cell cycle control
A. Types of genes associated with cancer:
 Genes that are normally responsible for growth factor production or their receptor formation as
well as molecules that are part of the intracellular cell signaling mechanisms as a response to
growth factors can lead to cancer if they are mutated.
 Some of these mutations can be spontaneous, but mostly caused by environmental factors
(mutagens) or viruses. Viruses can transfer the healthy genes to cancer causing genes by
inserting their DNA into the host cell’s DNA at the gene segment.
 The normal version of the genes that are responsible for growth factor production or signaling
are called proto-oncogenes because they normally code for proteins, but have the potential to
obtain cancer causing mutations and become oncogenes (cancer-causing genes).
 The genetic changes that can result in the formation of an oncogene can be the following:
o Movement of DNA within the genome (by viruses or by transposable elements
o Amplification of a proto-oncogene (formation of multiple copies of the same gene)
o Point mutation within the control element of the proto-oncogene or in the protooncogene itself

Cells normally also contain genes that are responsible for inhibiting cell division. These genes
are called tumor-suppressor genes because they code proteins that prevent uncontrolled cell
division. Any mutation on these genes can also result in cancer.
Summary:
Generally, more than one somatic mutation is necessary to produce all the changes necessary to have a
full-blown cancer. This may be the reason why the rates of cancer increase with age. There are
hundreds if not thousands of different types of cancer depending what is the path of mutations in the
cell. Here is an example of the development of colorectal cancer (no need to memorize this particular
pathway):
Unfortunately, it is also possible to inherit an oncogen or a mutant tumor-suppressor gene if these
mutations show up in the gametic cells of the parents. This is the reason why certain cancer types can
run in the families. The best-known inherited type of cancer is a form of breast cancer that is caused by
mutations in the BRCA1 or BRCA2 genes, that are normally function as tumor-suppressor genes.
KWL ON CHAPTER 19 (PAGES 359-374 ONLY) – EUKARYOTIC GENE EXPRESSION AND CANCER
Topics
Cell specialization and
differential gene
expression
Regulation of the
chromatin structure
Regulation of
transcription initiation
Mechanisms of posttranscriptional
regulation
Review: cancer
stages, treatment, cell
cycle control
Oncogenes and protooncogenes
Tumor-suppressor
genes
Overview of the
causes of cancer
K
What I know before
reading the chapter
W
What I want to find out
L
What I just learned
during the reading and
discussion