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

Fernandez-Justel, J. M.; Santa-Maria, C.; Ferrera-Lagoa, A.; Salinas-Pena, M.; Maslon, M. M.; Jordan, A.; Caceres, J. F.; Gomez, M.

doi:10.1101/2021.10.12.464039

bioRxiv · 10.1101/2021.10.12.464039

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

Fernandez-Justel, J. M.·Santa-Maria, C.·Ferrera-Lagoa, A.·Salinas-Pena, M.·Maslon, M. M.·Jordan, A.·Caceres, J. F.·Gomez, M.

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Abstract

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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Fernandez-Justel, J. M., Santa-Maria, C., Ferrera-Lagoa, A., Salinas-Pena, M., Maslon, M. M., Jordan, A., Caceres, J. F., Gomez, M.. 2021-10-12. Histone H1 regulates non-coding RNA turnover on chromatin in a m6A-dependent manner. https://doi.org/10.1101/2021.10.12.464039

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