Gene Silencing by Modification of HistonesSomanna 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.
Silencing in Yeast( S. Cerevisiae) • Silencing mediated by Deacetylation and Methylation Fig: Silencing at Yeast TelomereSIR proteins (Silent Information Regulation) form a silencing complex. This complex isrecruited by Rap1.
DNA methylation can recruit Histone Deacetylases and MethylasesDNA methyltransferase methylateCytosine within promoter. Thismodification binds proteins (MeCP2),which in turn recruit complexes modifyingnucleosome and switch off geneexpression. [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.