Control of Eukaryotic Gene Expression Flashcards
Regulation of gene expression at CHROMATIN level
- histone modification
- DNA methylation
Histone Acetylation
- histone acetyltransferases (HATs) add acetyl groups to positively-charged lysine residues on N-termini of histone tails; neutralise charges
- reduce electrostatic attraction between DNA and histones
- chromatin decondenses, increasing access to RNA polmerase and transcriptional machinery
- increase transcription
Histone Deacetylation
- histone deacetylases (HDACs) remove acetyl groups added by HATs
- increase electrostatic attraction between DNA and histones
- chromatin condenses to default condensed state, decreasing access to RNA polymerase and transcriptional machinery
- decreases transcription
DNA methylation
- DNA methlytransferases add methyl groups to cytosine residues in CpG islands
- chromatin condenses, decreasing access to RNA polymerase and transcriptional machinery
1) Methyl groups prevent transcriptional proteins from binding to promoter
2) Methyl-CpG- binding proteins recruit additional proteins (e.g HDACs) that suppress transcription
Regulation of gene expression at TRANSCRIPTIONAL level
- Control elements (promoter, enhancers, silencers)
- Proteins (TFs)
Role of promoters in regulating gene expression
- mediate binding of basal transcription factors and RNA polymerase to transcription start site, thereby allowing transcription to begin
Role of enhancers in regulating gene expression
- mediate binding of activators (specific TFs) and thus help to from transcription initiation complex
- increase rate of transcription
Role of silencers in regulating gene expression
- mediate binding of repressors (specific TFs) and thus help to from transcription initiation complex
- decrease rate of transcription
Properties of DISTAL control elements
- act over relatively long distances
- function independent of orientation
- function independent of position
Role of general/basal TFs in regulating gene expression
- TFIID 1st to bind to promoter; TATA binding protein recognises TATA box
- binding changes its own as well as DNA conformation
- mediates binding of other TFs before RNA polymerase binds to form transcription initiation complex
Role of specific TFs in regulating gene expression
- bind to respective distal control elements, influencing rate of transcription
Regulation of gene expression at POST-TRANSCRIPTIONAL level
- 5’ capping (7-methylguanosine cap)
- polyadenylation (addition of 3’ poly(A) tail)
- RNA splicing (introns excised, exons spliced together)
Functions of 5’ 7-methylguanosine cap
- prevent growing primary mRNA chain from being degraded by ribonucleases, RNAses
- facilitate export of mRNA from nucleus to cytoplasm
- recognition of mRNA by ribosomes for translation
Polyadenylation process
- cleavage recognise poly(A) signal sequence and bind to it
- pre-mRNA bends, stabilised by stabilising factors
- endonuclease recognises poly(A) signal and cuts downstream at the 3’ untranslated region
- poly(A) polymerase synthesises poly(A) tail by adding long sequence of adenine nucleotides at the 3’ end
Functions of poly(A) tail
- prevent pre-mRNA from being degraded by ribonucleases, RNAses
- facilitate export of mRNA from nucleus to cytoplasm
- recognition of mRNA by ribosomes for translation