Differential Gene Expression
Turning Genes on or keeping them off?
Differential Gene Regulation
• Transcriptional regulation
• Post-transcriptional regulation
• Translational regulation
• Post-translational regulation
Differential Gene Expression
• Transcriptional • Transcription factor binding
• Translational
• Transcription factor
interactions
• Post-translational
• Methylation
• Post-transcriptional
• Nucleosome/chromatin
structure
Differential Gene Expression
• Transcriptional
• Splicing
• Post-transcriptional • Polyadenylation
• Translational
• Post-translational
• Stability
Differential Gene Expression
• Transcriptional
• Masking
• Post-transcriptional
• Antisense RNA
• Translational
• Post-translational
Differential Gene Expression
• Transcriptional
• Glycosylation
• Post-transcriptional
• Acylation
• Translational
• Proteolytic processing
• Post-translational
Differential Gene Regulation
• Hierarchies of transcriptional regulatory
proteins
– Transcription Factors
• Regulators of regulators
Transcription
Initiation
Transcriptional Activation
Transcription Control Elements
• Promoter
– Basal elements (sites)
• TATAA box
• CCAAT box
• GC boxes
– Orientation and position dependent
• Enhancer
– Any combination of transcription factor binding sites
– Orientation and position independent
• Silencer
– Binding site for proteins which make DNA inaccessible
to txn factors
Transcription Factors
• Basal/General Txn Factors
– TFIID
• TBP - TATA binding protein
• TAFs – TBP associated factors
– CBP – CCAAT binding protein
– SP1 – GGCGGG binding protein
• Give a low level of txn
• Often found as the only txn control elements of
housekeeping genes
Transcription Factors
• Gene Specific Txn Factors
– Classified by DNA binding domains & mechanism of
transcriptional activation
Transcription Factor Flavors
Family
Homeodomain
Representative
Hox
POU
LIM
Paired Box
Hoxa-1, Antp, eve, en
Pit-1,Unc-86, Oct-2, Brn-5
Lim-1, Isl-1
Pax-1,2,6, Prd
Forkhead/Winged Helix
Fkh, HNF-3
Basic-helix-loop-helix
MyoD, Ac, da, emc
Basic leucine-zipper
Zinc-finger
AP1, Myc, C/EBP
standard
steroid receptors
WT-1, Krox-20, Kr, hb
GR, ER, RAR, kni
Sox
Sry, SoxD, Sox2
MADS box
MEF-1, MCM-1
Take A Look
www.devbio.com
Website 5.4
Physical Arrangement of
Regulatory Elements
Cell-Type Specific Transcription
• Tissue specificity
• Promoter
• Enhancer
• Tissue specific txn factor and cognizant
DNA element (site)
Epigenetic Gene Regulation
Differential Gene Expression Via
Posttranscriptional Regulation
Alternative or Differential Splicing
Differential Splicing
• Differential splicing requires cell-type
specific splicing factors
• Often one spliced mRNA does not encode a
functional protein
• When both alternative mRNAs encode
functional proteins, one protein typically
lacks an entire functional domain
Differential Splicing
Sex Determination in Drosophila Regulated by Differential Splicing
Differential Splicing & Sex
Girls
Boys
3’ UTR Mediates Stability or
Instability
U-Rich 3’UTR mediates
degradation of
Regulation of mRNA Stability
RNA masking and
Polyadenylation
• Factors bind to stored mRNA and prevent
translation
– smaug protein binds nanos mRNA
• mRNAs not polyadenylated
– deadenylated transcripts stable in oocyte
• Adenylation of transcript allows translation
Antisense RNA Regulates
Translation
Lin-4 RNA is complementary to
several regions of lin-14 3’ UTR
Formation of dsRNA prevents
translation of lin-14