Epigenetic control of cell cycle-dependent histone gene expression is a principal component of the abbreviated pluripotent cell cycle

Ricardo Medina, Prachi N. Ghule, Fernando Cruzat, A. Rasim Barutcu, Martin Montecino, Janet L. Stein, Andre J. van Wijnen, Gary S. Stein

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Self-renewal of human pluripotent embryonic stem cells proceeds via an abbreviated cell cycle with a shortened G1 phase. We examined which genes are modulated in this abbreviated period and the epigenetic mechanisms that control their expression. Accelerated upregulation of genes encoding histone proteins that support DNA replication is the most prominent gene regulatory program at the G1/S-phase transition in pluripotent cells. Expedited expression of histone genes is mediated by a unique chromatin architecture reflected by major nuclease hypersensitive sites, atypical distribution of epigenetic histone marks, and a region devoid of histone octamers. We observed remarkable differences in chromatin structure-hypersensitivity and histone protein modifications-between human embryonic stem (hES) and normal diploid cells. Cell cycle-dependent transcription factor binding permits dynamic three-dimensional interactions between transcript initiating and processing factors at 5' and 3' regions of the gene. Thus, progression through the abbreviated G1 phase involves cell cycle stage-specific chromatin-remodeling events and rapid assembly of subnuclear microenvironments that activate histone gene transcription to promote nucleosomal packaging of newly replicated DNA during stem cell renewal.

Original languageEnglish (US)
Pages (from-to)3860-3871
Number of pages12
JournalMolecular and cellular biology
Volume32
Issue number19
DOIs
StatePublished - Oct 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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