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Series GSE83495 Query DataSets for GSE83495
Status Public on Jul 27, 2017
Title A transcriptionally permissive histone H3 lysine 9 methylation state enables RNAi-mediated heterochromatin assembly
Organism Schizosaccharomyces pombe
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary 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.
Overall design ChIP-seq analysis of histone modifications and chromatin associated proteins
Contributor(s) Jih GT, Moazed D
Citation(s) 28682306
Submission date Jun 17, 2016
Last update date May 15, 2019
Contact name Gloria Jih
Organization name Harvard Medical School
Department Cell Biology
Lab Danesh Moazed
Street address 240 Longwood Ave, LHRRB 517
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
Platforms (1)
GPL13988 Illumina HiSeq 2000 (Schizosaccharomyces pombe)
Samples (71)
GSM2204423 H3K9me2_WT_SPY137
GSM2204424 H3K9me2_clr4Δ_SPY815
GSM2204425 H3K9me2_clr4F449Y_SPY4642
BioProject PRJNA326135
SRA SRP076738

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Supplementary file Size Download File type/resource
GSE83495_RAW.tar 2.3 Gb (http)(custom) TAR (of TDF)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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