CSB349H1 Lecture Notes - Lecture 8: Non-Coding Rna, Dicer, Heterochromatin

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Lecture 8(a): Heterochromatin & Positioning Effect
Heterochromatin:
1. Facultative Heterochromatin:
o Associated with repressed genes; can be turn on or off during development
§ H3K27me3
2. Constitutive Heterochromatin:
o Permanent silenced genes; repetitive sequences and transposons – can be
distinguished cytologically (i.e. Barr Body)
§ H3K9me3
Mechanisms for Heterochromatin Formation:
1. DNA-Sequence Dependent:
o Mechanisms rely on sequence specific DNA binding factors to recruit chromatin-
modifying complexes (i.e. MeCPs)
Active Genes:
DNA tend to be ‘open’ and allows access for TF and RNAP
to bind to the promotor and begin transcribing the gene
o Unmethylated DNA
Inactive Genes:
DNA is ‘silenced’ – proteins (MeCP2) bind to
methylated DNA and block the access of TF and
RNAP to the promoter
o Also recruit other proteins to induce heterochromatin formation (i.e. HMT)
2. RNA-Sequence Dependent:
a. Noncoding RNA (ncRNA) Mechanism
§ Two mechanisms:
(1) Xist - leading to the inactivation of X-chromosome
(2) Air imprinting of Igf2r cluster
X-Chromosome Inactivation:
One of the X-chromosomes will transcribe Xist to
generate ncRNA
o ncRNA will cluster the X-chromosome and
recruit other protein factors to modify DNA
and histones to condense the chromosome
ð Inactive X-chromosome is condensed with Barr-bodies
Air:
Similar mechanism by coating a region to silence
expression
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