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Histone H1 regulates non-coding RNA turnover on chromatin in a m6A-dependent manner

By José Miguel Fernández-Justel, Cristina Santa-María, Alberto Ferrera-Lagoa, Mónica Salinas-Pena, Magdalena M Maslon, Albert Jordan, Javier F Cáceres, María Gómez

Posted 12 Oct 2021
bioRxiv DOI: 10.1101/2021.10.12.464039

Linker histones are highly abundant chromatin-associated proteins with well-established structural roles in chromatin and as general transcriptional repressors. In addition, it has been long proposed that histone H1 exerts context-specific effects on gene expression. Here, we have identified a new function of histone H1 in chromatin structure and transcription using a range of genomic approaches. We show that histone H1-depleted cells accumulate nascent non-coding RNAs on chromatin, suggesting that histone H1 prevents non-coding RNA transcription and regulates non-coding transcript turnover on chromatin. Accumulated non-coding transcripts have reduced levels of m6A modification and cause replication-transcription conflicts. Accordingly, altering the m6A RNA methylation pathway rescues the replicative phenotype of H1 loss. This work unveils unexpected regulatory roles of histone H1 on non-coding RNA turnover and m6A deposition, highlighting the intimate relationship between chromatin conformation, RNA metabolism and DNA replication to maintain genome performance.

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