Gene expression II Flashcards
in chromatin, the dna to protein ratio is aproximately… ?
1:1
Two classes of chromatin remodelling factors:
- DNA dependent ATPases (SWI/SNF): disrupt histone octamers and DNA
- Factors that reversably modify histones through acetylation (HATs and HDACs)
what is the basic structural unit of chromatin?
nucleosome: core histone proteins around which DNA is wound
where are histones modified?
n-termini
-rich in lysine residues which can be motified by acetylation, phosphorylation, methylation, and ubiquitination
what is acetylation associated with?
gene control
what can activators and repressors recruit?
HATS or HDACS
What do HATs do?
acetylate n-termini of histones
What do HDACs do?
remove acetyl groups from histones
histones retain positive charge at n-terminal ends
Original understanding of HATs
-neutralizes positively charged ends and eliminate electrostatic interactions with DNA phosphates: DNA opened for general transcription factors/ pol II transcriptional apparatus
Original understanding of HDACs
maintain access with DNA to prevent access of transcription factors to promoter
Current understanding of HATs
acetylation of lysines allow binding of specific transcription factors
patterns of histone acetylation…
recruit different factors that will affect transcriptional state
Overall, HATS are ________, and HDACs are ________.
HATS are co-activators
HDACs are co-repressors
________ are examples of ________ that can switch from repressors to activators by recruiting either HATs of HDAVs.
thyroid hormone receptors
trans-acting factors
Rubinstein taybi syndrome frequency and phenotype
1/125,000
growth retardation, mental retardation, craniofacial dysmorphism, abnormally broad thumbs and great toes
cause of rubinstein taybi syndrome
mutations in one copy of CREB binding protein (CBP)
CBP: transcriptional coactivator for many transcription factors and is a histone acetyltransferase
character of mutation in rubinstein taybi syndrome
normally recruited to many genes to activate transcription
haploinsufficiency can result in widespread transcriptional changes
some causes of leukemia
chromosomal translocations leading to gain of function fusion proteins
can involve fusion of transcriptional regulators with HATs or HDACs and alter activity of regulators
two ways transcriptional activators and repressors work
- interact with general transcription factors/ polymerase II associated proteins to influence initiation of elongation of the primary transcript
- interact with chromatin to regulate accessibility of DNA to Pol II transcriptional apparatus
specificity depends on…
binding of transcriptional activators/ repressors to DNA control elements
regulations depends on…
DNA protein and protein-protein interactions
Interactions affect…
conformation of DNA
modification of chromatin structure
formation of transcription initiation complex
control is ________.
combinatorial
