1. Gene Silencing
by
Modification of Histones
Somanna A. N.

2. Gene Silencing
• Gene silencing is a general term
describing epigenetic processes of gene regulation.
• Silencing is a position effect.
• Silencing can spread over large stretches of DNA
• Transcriptional gene silencing is the result
of histone modifications, creating an environment
of heterochromatin around a gene that makes it inaccessible
to transcriptional machinery.

3. Histone Tail Modification Status Correlates with
Transcriptional Activity

4. Acetylation
• These reactions are catalyzed by enzymes with "histone
acetyltransferase" (HAT) or "histone deacetylase" (HDAC) activity.
• It also reduces affinity of tail for adjacent nucleosomes, thus
affecting ability of nucleosome arrays to form more repressive
higher-ordered chromatin structures.

5. Methylation
• These reactions are catalyzed by enzymes "histone
methyltransferase”
• Methylation recruit silencing or regulatory proteins that bind
methylated histones.
• Chromodomain containing proteins interact with methylated
histone tails.

6. Histone Acetylation and Methylation

7. Silencing in Yeast( S. Cerevisiae)
• Silencing mediated by Deacetylation and Methylation
Fig: Silencing at Yeast Telomere
SIR proteins (Silent Information Regulation) form a silencing complex. This complex is
recruited by Rap1.

8. DNA methylation can recruit Histone
Deacetylases and Methylases
DNA methyltransferase methylate
Cytosine within promoter. This
modification binds proteins (MeCP2),
which in turn recruit complexes modifying
nucleosome and switch off gene
expression. [In Mammals]

9. Epigenetic Inheritence of Nucleosome
Modification
• These modifications recruit enzymes
that perform same modifications
and thus propogate the state of
modification to daughter
chromosomes.