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

José Miguel Fernández-Justel, Cristina Santa-María, Sara Martín-Vírgala, Shreya Ramesh, Alberto Ferrera-Lagoa, Mónica Salinas-Pena, Javier Isoler-Alcaraz, Magdalena Maslon, Albert Jordan, Javier F. Caceres, María Gómez*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 identify a function of histone H1 in chromatin structure and transcription using a range of genomic approaches. In the absence of histone H1, there is an increase in the transcription of non-coding RNAs, together with reduced levels of m6A modification leading to their accumulation on chromatin and causing replication-transcription conflicts. This strongly suggests that histone H1 prevents non-coding RNA transcription and regulates non-coding transcript turnover on chromatin. 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.

Original languageEnglish
JournalCell Reports
Volume40
Issue number11
DOIs
Publication statusPublished - 13 Sept 2022

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