Gene Silencing by

Modification of Histones

Somanna A. N.

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.

Histone Tail Modification Status Correlates with Transcriptional Activity

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.

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.

Histone Acetylation and Methylation

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.

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]

Epigenetic Inheritence of Nucleosome Modification

• These modifications recruit enzymes that perform same modifications and thus propogate the state of modification to daughter chromosomes.