Eukaryotic Gene Regulation 2 Flashcards
histone proteins
H2A, H2B, H3, H4 (histone core) + H1
how can chromatin structure affect transcription (3)
- nucleosomes = make promoters/enhancers inaccessible to RNA pol & transcription factors
- histone modification = how tight DNA w nucleosomes
- chromatin remodelling (caused by DNA methylation)
what about histones can be modified
+ 4 ways it can be modified
N-terminal tails (H3 and H4)
methylation, acetylation, phosphorylation, ubiquitination
active marker
open chromatin
H4K16Ac
repressive marker
compact chromatin
H3K27Me
lysine acetylation on histone tail
positive charge is lost on side chain amino group = decreases electrostatic interaction w DNA negative phosphate groups of DNA backbone
remodelling proteins (complexes)
DNA at promoters & enhancers becomes more accessible to TFs
can be assayed using DNase digestion
SWI-SNF remodeling complex
uses E from AT hydrolysis to alter nucleosome positioning
the 3 levels of post-transcriptional regulation of gene expression
- mRNA (splicing, editing, stability/turnover, localisation)
- translation
- protein (stability/turnover, localisation, post translation modification PTM)
alternative splicing
splicing of primary transcript into mRNAs that encode different proteins
same script can produce diff proteins depending on how its spliced
rate of mRNA turnover depends on…
rate of synthesis & degradation
longer life of mRNA = more protein can be produced
what affects the lifespan of mRNA (2)
- cap & poly A tail (protects against RNases)
- regulatory elements in UTRs (promote mRNA degradation)
two types of small RNAs
- siRNA → synthetic/exogenous
- miRNA → endogenous genome-encoded molecule
miRNAs
- transcribed by RNA pol II
- generate short dsRNA hairpins
drosha
excises stem-loop from primary mRNA to generate pre-miRNA
specialised RNase