Histone deacetylases govern heterochromatin in every phase

Abstract

EMBO J 32 17, 2321–2325 doi:; DOI: 10.1038/emboj.2013.143; published online June 14 2013

Deacetylation of histone tails has been shown to play a role during heterochromatin formation, but the precise mechanism of action has not been understood. Complementary results presented in two recent articles in The EMBO Journal (Alper et al, 2013; Buscaino et al, 2013) together reveal how histone deacetylases (HDACs) affect the various phases of heterochromatin formation: establishment, maintenance and spreading.

Figure 1

Roles of the HDACs Sir2 and Clr3 in pericentromeric heterochromatin formation. (A) Sir2 and Clr3, together with Swi6^HP1, contribute to all phases of heterochromatin formation: establishment, spreading and maintenance. They do so by enhancing the action of the histone methyltransferase Clr4, which promotes heterochromatin formation via methylation of Lys9 of histone H3 (H3K9). Clr4 is recruited by RNAi-dependent and RNAi-independent mechanisms during the establishment phase, and Sir2 and/or Clr3 is required for both these mechanisms. During spreading and maintenance, the mechanism for the recruitment of Clr4 is not well understood. (B) Mechanisms of Sir2 to assist Clr4 function. Acetylation of H3K9 as well as H3K14 may specifically inhibit the action of Clr4 to methylate H3K9. In addition, the histone acetylation enhances transcription by RNA polymerase II (RNA pol II), which is associated with an elevated rate of histone turnover that prevents Clr4 from stably methylating H3K9. Sir2 and Clr3 cancel the inhibitory effects of the H3 acetylation by deacetylating H3K9 and 14.