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The histone variant H2A.Z promotes splicing of weak introns (array)

ABSTRACT: Multiple lines of evidence implicate chromatin in the regulation of pre-mRNA splicing. However, the influence of chromatin factors on co-transcriptional splice-site usage remains unclear. Here we investigated the function of the highly conserved histone variant H2A.Z in pre-mRNA splicing using the intron-rich model yeast, Schizosaccharomyces pombe. Using Epistatic Mini-Array Profiles (EMAPs) to survey the genetic interaction landscape of the Swr1 nucleosome remodeling complex, which deposits H2A.Z, we uncovered evidence for functional interactions with components of the spliceosome. In support of these genetic connections, splicing-specific microarrays show that H2A.Z and the Swr1 ATPase are required during temperature stress for the efficient splicing of a sub-set of introns. Notably, affected introns are enriched for H2A.Z occupancy, and more likely to contain non-consensus splice sites. To test the significance of the latter correlation, we mutated the splice sites in an affected intron to consensus and found this suppressed the requirement for H2A.Z in splicing of that intron. These data suggest that H2A.Z occupancy promotes co-transcriptional splicing of sub-optimal introns that may otherwise be discarded via proofreading ATPases. Consistent with this model, we show that over-expression of splicing ATPase Prp16 suppresses both the growth and splicing defects seen in the absence of H2A.Z.

ORGANISM(S): Schizosaccharomyces pombe

PROVIDER: GSE97983 | GEO | 2017/08/22

SECONDARY ACCESSION(S): PRJNA383571

REPOSITORIES: GEO

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The histone variant H2A.Z promotes splicing of weak introns (ChIP-Seq)

Project description:Multiple lines of evidence implicate chromatin in the regulation of pre-mRNA splicing. However, the influence of chromatin factors on co-transcriptional splice-site usage remains unclear. Here we investigated the function of the highly conserved histone variant H2A.Z in pre-mRNA splicing using the intron-rich model yeast, Schizosaccharomyces pombe. Using Epistatic Mini-Array Profiles (EMAPs) to survey the genetic interaction landscape of the Swr1 nucleosome remodeling complex, which deposits H2A.Z, we uncovered evidence for functional interactions with components of the spliceosome. In support of these genetic connections, splicing-specific microarrays show that H2A.Z and the Swr1 ATPase are required during temperature stress for the efficient splicing of a sub-set of introns. Notably, affected introns are enriched for H2A.Z occupancy, and more likely to contain non-consensus splice sites. To test the significance of the latter correlation, we mutated the splice sites in an affected intron to consensus and found this suppressed the requirement for H2A.Z in splicing of that intron. These data suggest that H2A.Z occupancy promotes co-transcriptional splicing of sub-optimal introns that may otherwise be discarded via proofreading ATPases. Consistent with this model, we show that over-expression of splicing ATPase Prp16 suppresses both the growth and splicing defects seen in the absence of H2A.Z.

2017-08-22 | GSE97982 | GEO

The histone variant H2A.Z promotes efficient co-transcriptional splicing in S. cerevisiae

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