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The RSC complex localizes to coding sequences to regulate Pol II and histone occupancy.

ABSTRACT: ATP-dependent chromatin remodelers regulate chromatin structure during multiple stages of transcription. We report that RSC, an essential chromatin remodeler, is recruited to the open reading frames (ORFs) of actively transcribed genes genome wide, suggesting a role for RSC in regulating transcription elongation. Consistent with such a role, Pol II occupancy in the ORFs of weakly transcribed genes is drastically reduced upon depletion of the RSC catalytic subunit Sth1. RSC inactivation also reduced histone H3 occupancy across transcribed regions. Remarkably, the strongest effects on Pol II and H3 occupancy were confined to the genes displaying the greatest RSC ORF enrichment. Additionally, RSC recruitment to the ORF requires the activities of the SAGA and NuA4 HAT complexes and is aided by the activities of the Pol II CTD Ser2 kinases Bur1 and Ctk1. Overall, our findings strongly implicate ORF-associated RSC in governing Pol II function and in maintaining chromatin structure over transcribed regions.

SUBMITTER: Spain MM

PROVIDER: S-EPMC4258446 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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The RSC complex localizes to coding sequences to regulate Pol II and histone occupancy.

Spain Marla M MM Ansari Suraiya A SA Pathak Rakesh R Palumbo Michael J MJ Morse Randall H RH Govind Chhabi K CK

Molecular cell 20141106 5

ATP-dependent chromatin remodelers regulate chromatin structure during multiple stages of transcription. We report that RSC, an essential chromatin remodeler, is recruited to the open reading frames (ORFs) of actively transcribed genes genome wide, suggesting a role for RSC in regulating transcription elongation. Consistent with such a role, Pol II occupancy in the ORFs of weakly transcribed genes is drastically reduced upon depletion of the RSC catalytic subunit Sth1. RSC inactivation also redu ...[more]

PMID: 25457164

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Project description:BackgroundApplying supervised learning/classification techniques to epigenomic data may reveal properties that differentiate histone modifications. Previous analyses sought to classify nucleosomes containing histone H2A/H4 arginine 3 symmetric dimethylation (H2A/H4R3me2s) or H2A.Z using human CD4+ T-cell chromatin immunoprecipitation sequencing (ChIP-Seq) data. However, these efforts only achieved modest accuracy with limited biological interpretation. Here, we investigate the impact of using appropriate data pre-processing -deduplication, normalization, and position- (peak-) finding to identify stable nucleosome positions - in conjunction with advanced classification algorithms, notably discriminatory motif feature selection and random forests. Performance assessments are based on accuracy and interpretative yield.ResultsWe achieved dramatically improved accuracy using histone modification features (99.0%; previous attempts, 68.3%) and DNA sequence features (94.1%; previous attempts, <60%). Furthermore, the algorithms elicited interpretable features that withstand permutation testing, including: the histone modifications H4K20me3 and H3K9me3, which are components of heterochromatin; and the motif TCCATT, which is part of the consensus sequence of satellite II and III DNA. Downstream analysis demonstrates that satellite II and III DNA in the human genome is occupied by stable nucleosomes containing H2A/H4R3me2s, H4K20me3, and/or H3K9me3, but not 18 other histone methylations. These results are consistent with the recent biochemical finding that H4R3me2s provides a binding site for the DNA methyltransferase (Dnmt3a) that methylates satellite II and III DNA.ConclusionsClassification algorithms applied to appropriately pre-processed ChIP-Seq data can accurately discriminate between histone modifications. Algorithms that facilitate interpretation, such as discriminatory motif feature selection, have the added potential to impart information about underlying biological mechanism.

Dataset Information

The RSC complex localizes to coding sequences to regulate Pol II and histone occupancy.

Publications

The RSC complex localizes to coding sequences to regulate Pol II and histone occupancy.

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