Pre-mRNA splicing is a determinant of histone H3K36 methylation

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Abstract

A chromatin code appears to mark introns and exons with distinct patterns of nucleosome enrichment and histone methylation. We investigated whether a causal relationship exists between splicing and chromatin modification by asking whether splice-site mutations affect the methylation of histone H3K36. Deletions of the 3′splice site in intron 2 or in both introns 1 and 2 of an integrated β-globin reporter gene caused a shift in relative distribution of H3K36 trimethylation away from 5′ ends and toward 3′ ends. The effects of splice-site mutations correlated with enhanced retention of a U5 snRNP subunit on transcription complexes downstream of the gene. In contrast, a poly(A) site mutation did not affect H3K36 methylation. Similarly, global inhibition of splicing by spliceostatin A caused a rapid repositioning of H3K36me3 away from 5′ ends in favor of 3′ ends. These results suggest that the cotranscriptional splicing apparatus influences establishment of normal patterns of histone modification.

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Kim, S., Kim, H., Fong, N., Erickson, B., & Bentley, D. L. (2011). Pre-mRNA splicing is a determinant of histone H3K36 methylation. Proceedings of the National Academy of Sciences of the United States of America, 108(33), 13564–13569. https://doi.org/10.1073/pnas.1109475108

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