Transcription-associated histone pruning demarcates macroH2A chromatin domains

Zhen Sun, Dan Filipescu, Joshua Andrade, Alexandre Gaspar-Maia, Beatrix Ueberheide, Emily Bernstein

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


The histone variant macroH2A occupies large repressive domains throughout the genome; however, mechanisms underlying its precise deposition remain poorly understood. Here, we characterize de novo chromatin deposition of macroH2A2 using temporal genomic profiling in murine-derived fibroblasts devoid of all macroH2A isoforms. We find that macroH2A2 is first pervasively deposited genome wide at both steady-state domains and adjacent transcribed regions, the latter of which are subsequently pruned, establishing mature macroH2A2 domains. Pruning of macroH2A2 can be counteracted by chemical inhibition of transcription. Further, locus-specific transcriptional manipulation reveals that gene activation depletes pre-existing macroH2A2, while silencing triggers ectopic macroH2A2 accumulation. We demonstrate that the FACT (facilitates chromatin transcription) complex is required for macroH2A2 pruning within transcribed chromatin. Taken together, we have identified active chromatin as a boundary for macroH2A domains through a transcription-associated ‘pruning’ mechanism that establishes and maintains the faithful genomic localization of macroH2A variants.

Original languageEnglish (US)
Pages (from-to)958-970
Number of pages13
JournalNature Structural and Molecular Biology
Issue number10
StatePublished - Oct 1 2018

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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