CSB349H1 Lecture Notes - Lecture 3: Histone Acetyltransferase, Histone Deacetylase, Histone Methyltransferase
14 May 2018
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“- - -“ lines represent histone tails
Lecture 3(c): Transcription
Transcriptional Control:
• For any gene expression to occur, we require RNAP to the 5’ end
of the gene and begin transcribing the mRNA
o RNAP cannot bind to condensed chromatin; it requires
an uncondensed, relaxed DNA with no chromatin
§ How does this occur?
Chromatin Remodeling:
• Two classes of enzymes function in remodeling the chromatin:
i. Class I
§ Covalent modification of histone proteins
• Modifications
indirectly
regulate chromatic structure through
recruitment of chromatin-associated proteins
ii. Class II
§ Additional recruitment of ATP-dependent nucleosome multiprotein
remolding complex
•
Directly
overcome the repressive nature of nucleosomes
ð Both enzymes require ATP
o Class I => Use ATP to chemically modify the nucleosomes
o Class II => Use ATP to physically modify the chromatin
Chemical Modification:
• Chemical modification of histones tails within nucleosomes; histones contain:
o Globular domain that interacts with other histone proteins and DNA
o Flexible tail region (N and C terminus), which acts as a substrate for post-translational
modifications
• Chemical modifications include:
o Acetylation, methylation, phosphorylation and
ubiquitination on the protruding N-terminal tail
ð Distinct modifications correlate with specific
transcriptional states
o Which histone, what covalent modification &
what position in the histone tail was modified
ð Proteins that are recruited due to the chemical modifications include: transcription factors,
ATP-dependent nucleosomal remodeling enzymes and other histone modifying enzymes
ð Class I enzymes are referred to as the writer and eraser of the marks (chemical modifications)
o Histone acetyltransferase (HAT) <=> Histone deacetylase (HDAC)
o Histone methyltransferase (HMT) <=> Histone demethylase (HDM)
o Histone kinase <=> Histone phosphatase
o Histone ubiquitin ligase <=> Histone deubiquitinase
Complex of proteins along with the
enzyme that functions in the
chemical modification
Class I enzymes are multiprotein
complexes
Document Summary
Chromatin remodeling: two classes of enzymes function in remodeling the chromatin, class i. Covalent modification of histone proteins: modifications indirectly regulate chromatic structure through recruitment of chromatin-associated proteins, class ii. Additional recruitment of atp-dependent nucleosome multiprotein remolding complex: directly overcome the repressive nature of nucleosomes. Both enzymes require atp: class i => use atp to chemically modify the nucleosomes, class ii => use atp to physically modify the chromatin. Distinct modifications correlate with specific transcriptional states: which histone, what covalent modification & what position in the histone tail was modified. Proteins that are recruited due to the chemical modifications include: transcription factors, Atp-dependent nucleosomal remodeling enzymes and other histone modifying enzymes. Complex of proteins along with the enzyme that functions in the chemical modification. Question : how can we identify the different chemical histone modifications an enzyme does, capable of identifying modifications by chromatin immunoprecipitation (chip)
