Department of Cell Biology and Cancer Center
Self-renewal of human pluripotent embryonic stem cells proceeds via an abbreviated cell cycle with a shortened G(1) 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 G(1)/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 G(1) 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.
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DOI of Published Version
Mol Cell Biol. 2012 Oct;32(19):3860-71. doi: 10.1128/MCB.00736-12. Epub 2012 Jul 23. Link to article on publisher's website
Molecular and cellular biology
Medina, Ricardo F.; Ghule, Prachi N.; Cruzat, Fernando; Barutcu, Ahmet Rasim; Montecino, Martin A.; Stein, Janet L.; Van Wijnen, Andre J.; and Stein, Gary S., "Epigenetic control of cell cycle-dependent histone gene expression is a principal component of the abbreviated pluripotent cell cycle" (2012). GSBS Student Publications. 2007.