Human histone H1 variants impact splicing outcome by controlling RNA polymerase II elongation

Corina Pascal, Jonathan Zonszain, Ofir Hameiri, Chen Gargi-Levi, Galit Lev-Maor, Luna Tammer, Tamar Levy, Anan Tarabeih, Vanessa Rachel Roy, Stav Ben-Salmon, Liraz Elbaz, Mireille Eid, Tamar Hakim, Salima Abu Rabe'a, Nana Shalev, Albert Jordan, Eran Meshorer, Gil Ast*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Histones shape chromatin structure and the epigenetic landscape. H1, the most diverse histone in the human genome, has 11 variants. Due to the high structural similarity between the H1s, their unique functions in transferring information from the chromatin to mRNA-processing machineries have remained elusive. Here, we generated human cell lines lacking up to five H1 subtypes, allowing us to characterize the genomic binding profiles of six H1 variants. Most H1s bind to specific sites, and binding depends on multiple factors, including GC content. The highly expressed H1.2 has a high affinity for exons, whereas H1.3 binds intronic sequences. H1s are major splicing regulators, especially of exon skipping and intron retention events, through their effects on the elongation of RNA polymerase II (RNAPII). Thus, H1 variants determine splicing fate by modulating RNAPII elongation.

Original languageAmerican English
Pages (from-to)3801-3817.e8
JournalMolecular Cell
Volume83
Issue number21
DOIs
StatePublished - 2 Nov 2023

Bibliographical note

Publisher Copyright:
© 2023 Elsevier Inc.

Keywords

  • ChIP-seq
  • GC content
  • H1 histones
  • PRO-seq
  • RNA polymerase II elongation
  • RNA-seq
  • alternative splicing
  • exon skipping
  • intron retention

Fingerprint

Dive into the research topics of 'Human histone H1 variants impact splicing outcome by controlling RNA polymerase II elongation'. Together they form a unique fingerprint.

Cite this