Dataset Information

A Composite DNA Element that Functions as a Maintainer Required for Epigenetic Inheritance of Heterochromatin

ABSTRACT: Epigenetic inheritance of heterochromatin requires DNA sequence-independent propagation mechanisms, coupling to RNAi, or input from DNA sequence, but how DNA contributes to inheritance is not understood. Here, we identify a DNA element (termed “maintainer”) that is sufficient for epigenetic inheritance of preexisting histone H3 lysine 9 methylation (H3K9me) and heterochromatin in Schizosaccharomyces pombe, but cannot establish de novo gene silencing in wild-type cells. This maintainer is a composite DNA element with binding sites for the Atf1/Pcr1 and Deb1 transcription factors and the Origin Recognition Complex (ORC), located within a 130-base pair region, and can be converted to a silencer in cells with lower rates of H3K9me turnover, suggesting that it participates in recruiting the H3K9 methyltransferase Clr4/Suv39h. These results suggest that, in the absence of RNAi, histone H3K9me is only heritable when it can collaborate with maintainer-associated DNA-binding proteins that help recruit the enzyme responsible for its epigenetic deposition.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Schizosaccharomyces Pombe 927

SUBMITTER: Joao Paulo

LAB HEAD: Danesh Moazed

PROVIDER: PXD027214 | Pride | 2022-10-14

REPOSITORIES: Pride

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			Action	DRS
	TableS4_No3_j31110.mzIdentML	Mzid
	TableS4_No3_j31110.raw	Raw
	TableS4_No4_j31110_724.mzIdentML	Mzid
	TableS4_No4_j31110_724.raw	Raw
	TableS4_No5__j31110_023.mzIdentML	Mzid

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A composite DNA element that functions as a maintainer required for epigenetic inheritance of heterochromatin.

Wang Xiaoyi X Paulo Joao A JA Li Xue X Zhou Haining H Yu Juntao J Gygi Steven P SP Moazed Danesh D

Molecular cell 20210809 19

Epigenetic inheritance of heterochromatin requires DNA-sequence-independent propagation mechanisms, coupling to RNAi, or input from DNA sequence, but how DNA contributes to inheritance is not understood. Here, we identify a DNA element (termed "maintainer") that is sufficient for epigenetic inheritance of pre-existing histone H3 lysine 9 methylation (H3K9me) and heterochromatin in Schizosaccharomyces pombe but cannot establish de novo gene silencing in wild-type cells. This maintainer is a compo ...[more]

PMID: 34375584

Similar Datasets

Project description:Heterochromatic DNA domains play important roles in the regulation of gene expression and maintenance of genome stability by silencing repetitive DNA elements and transposons. In organisms ranging from fission yeast to mammals, heterochromatin assembly at DNA repeats involves the activity of small noncoding RNAs (sRNAs) associated with the RNA interference (RNAi) pathway. Typically, sRNAs, originating from long noncoding RNAs transcribed from DNA repeats, guide Argonaute-containing effector complexes to complementary nascent RNAs to initiate histone H3 lysine 9 di- and tri-methylation (H3K9me2 and H3K9me3, respectively) and heterochromatin formation. H3K9me is in turn required for recruitment of RNAi to chromatin and promotes sRNA generation. However, how heterochromatin formation, which silences transcription, can proceed by a co-transcriptional mechanism that also promotes sRNA generation remains paradoxical. Here, using Clr4, the fission yeast homolog of mammalian SUV39H H3K9 methyltransferases, we designed active site mutations, which allow H3K9me2 catalysis but block the transition to H3K9me3. We show that H3K9me2 defines a functionally distinct heterochromatin state that is sufficient for RNAi-dependent co-transcriptional gene silencing (CTGS). Unlike H3K9me3 domains, which are transcriptionally silent, H3K9me2 domains are transcriptionally active, contain modifications associated with euchromatic transcription, and couple RNAi-mediated transcript degradation to the establishment of H3K9me domains. The two H3K9me states recruit reader proteins with different efficiencies, explaining their different downstream silencing functions. Furthermore, transition from H3K9me2 to H3K9me3 is required for RNAi-independent epigenetic inheritance of H3K9me domains. Our findings demonstrate that H3K9me2 and H3K9me3 define functionally distinct heterochromatin states and uncover a mechanism for formation of transcriptionally permissive heterochromatin that is compatible with its broadly conserved role in RNAi-mediated genome defense.