Abstract
It is important to accurately regulate the expression of genes involved in development and environmental response. In the fission yeast Schizosaccharomyces pombe, meiotic genes are tightly repressed during vegetative growth. Despite being embedded in heterochromatin these genes are transcribed and believed to be repressed primarily at the level of RNA. However, the mechanism of facultative heterochromatin formation and the interplay with transcription regulation is not understood. We show genome-wide that HDAC-dependent histone deacetylation is a major determinant in transcriptional silencing of facultative heterochromatin domains. Indeed, mutation of class I/II HDACs leads to increased transcription of meiotic genes and accumulation of their mRNAs. Mechanistic dissection of the pho1 gene where, in response to phosphate, transient facultative heterochromatin is established by overlapping lncRNA transcription shows that the Clr3 HDAC contributes to silencing independently of SHREC, but in an lncRNA-dependent manner. We propose that HDACs promote facultative heterochromatin by establishing alternative transcriptional silencing.
Highlights
Heterochromatin is critical to eukaryotic cells and exists in two functionally distinct forms: constitutive and facultative heterochromatin
Using the pho1 locus as a model of facultative heterochromatin, we demonstrate that transcription is derepressed upon inhibition of class I/II HDACS using trichostatin A (TSA)
The class II histone deacetylase complexes (HDACs) Clr3 contributes to pho1 silencing
Summary
Heterochromatin is critical to eukaryotic cells and exists in two functionally distinct forms: constitutive and facultative heterochromatin. Chromatin modifying complexes play a central role in heterochromatin formation These include the Clr4/Suv39h-methyltransferase complex (CLRC) that methylates Lys of histone H3 (H3K9me), as well as the class I (Clr and Hos2), class II (Clr3) and class III (Sir, NAD+-dependent, ‘sirtuins’) histone deacetylase complexes (HDACs). Heterochromatic ncRNAs are converted into dsRNAs through the action of the RNA-directed RNA polymerase complex (RDRC) and subsequently cleaved by the ribonuclease III Dicer (Dcr1) to produce small interfering RNAs (siRNAs) of 21–23 nucleotides [6,7,8] These siRNAs are converted into single-stranded siRNAs and, together with Argonaut proteins, form the RNA-induced transcriptional silencing (RITS) complex. The Clr H3K9me mark, in turn, acts as a landing platform for the HP1-like proteins Swi and Chp2 [7] These proteins target class I and II HDAC complexes, leading to further compaction of heterochromatin and transcriptional gene silencing [11]. SHREC has been shown to be recruited to pericentromeric heterochromatin by the conserved protein Seb
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