title: Epigenetic control of cell cycle-dependent histone gene expression is a principal component of the abbreviated pluripotent cell cycle.
abstract: 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.
authors: Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, MA, USA.
authors: Ricardo
authors: R
authors: Medina
authors: Prachi N
authors: PN
authors: Ghule
authors: Fernando
authors: F
authors: Cruzat
authors: A Rasim
authors: AR
authors: Barutcu
authors: Martin
authors: M
authors: Montecino
authors: Janet L
authors: JL
authors: Stein
authors: Andre J
authors: AJ
authors: van Wijnen
authors: Gary S
authors: GS
authors: Stein
mesh_terms: D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D003851:Deoxyribonucleases / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D044127:Epigenesis, Genetic; D016193:G1 Phase; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D016196:S Phase; D015854:Up-Regulation
chemical_list: D002843:Chromatin; C442219:HINFP protein, human; D006657:Histones; D012097:Repressor Proteins; D012319:RNA Polymerase II; D003851:Deoxyribonucleases