Chromatin remodelling and modification Flashcards
why eukaryotic gene are off in ground state?
Heterochromatin: highly compressed and not transcribed
Regulatory elements is hidden from the regulatory gene
Chromatin structure can be altered by
– Histone protein tail acetylation
– DNA methylation
– SWI-SNF chromatin remodelling protein complex
Packaging of eukaryotic DNA into chromatin
– Regulatory sequences required for transcription
(promoter, promoter-proximal elements and
enhancers) are inaccessible for most of the
genes
Chromatin remodeling exposes regulatory sequence
Shifting of DNA along the nucleosome in such away where the promotor is exposed for regulatory protein binding
How does modification of histone effect gene expression?
Modification of histones (acetylation,
methylation) controls gene expression
via different mechanisms
Acetylation of histone tails
• Acetylation (CH3CO) of histone tails stops
interaction with neighboring nucleosome and DNA
Histone tails
• Histone proteins have amino acids “tails” which
stick out of the nucleosome
• The histone tails can bind next nucleosome and
adjacent DNA
– Favourable electrostatic interactions between Lys
residues of the tails (+) and:
• negatively charged pocket on the adjacent nucleosome
• negatively charged phosphate backbone of the surrounding DNA
– Stabilises condensed structure
De-acetylated histone tail
De-acetylated Favors condensation—> Represses transcription —> Gene inactive
positively charged tail is attracted to the negatively charged surface of histone
Positively charged tail is attracted to the negatively charged phosphate backbone of the DNA
Acetylated histone tail
Acetylated —-> Stops condensation—-> Favors transcription—-> Gene active
Acetyl removes the positive charge on the tail and become neutral —> nucleosome dissociates
Acetylation of histone
Reversible
• HAT = enzyme histone acetyltransferase
• HDAC = enzyme histone deacetylase
Regulation by histone acetylation
How does the level of acetylation effect the gene expression?
Level of histone acetylation affects gene
expression
– More acetylation = more transcription
– Less acetylation = less transcription
Regulation by histone acetylation
- increasing acetylation
Some eukaryotic activator protein complexes
direct acetylation of histones near promoters
– Opens chromatin structure and increases gene
transcription
Regulation by histone acetylation
- decreasing acetylation
• Some eukaryotic repressor protein complexes
direct de-acetylation of histones near promoters
– Compresses chromatin structure and reduces gene
transcription (as is the case for the yeast GAL genes
in the presence of glucose, the preferred substrate
what happens in presence of glucose and galactose to GAL gene expression?
In presence of galactose and glucose, the transcription of GAL1 is repressed regardless of presence of activator GAL 4 on the UAS
Mig1 repressor binds between UAS and promoter and recruits Tup1 that has an HDAC activity.
DNA becomes deacetylated in this region, turning the gene transcription off
Methylation of histone tail
Lysines and arginines
• HMTase = enzyme histone methyltransferase
• Does not affect the charge
• Creates binding sites for either activator or
repressor proteins
– Depends on the residues modified
• Can activate or repress gene expression
