H2A.Z maintenance during mitosis reveals nucleosome shifting on mitotically silenced genes.
Profound chromatin changes occur during mitosis to allow for gene silencing and chromosome segregation followed by reactivation of memorized transcription states in daughter cells. Using genome-wide sequencing, we found H2A.Z-containing +1 nucleosomes of active genes shift upstream to occupy TSSs during mitosis, significantly reducing nucleosome-depleted regions. Single-molecule analysis confirmed nucleosome shifting and demonstrated that mitotic shifting is specific to active genes that are silenced during mitosis and, thus, is not seen on promoters, which are silenced by methylation or mitotically expressed genes. Using the GRP78 promoter as a model, we found H3K4 trimethylation is also maintained while other indicators of active chromatin are lost and expression is decreased. These key changes provide a potential mechanism for rapid silencing and reactivation of genes during the cell cycle.
Kelly
Theresa K
TK
Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Miranda
Tina Branscombe
TB
Liang
Gangning
G
Berman
Benjamin P
BP
Lin
Joy C
JC
Tanay
Amos
A
Jones
Peter A
PA
D000107:Acetylation; D023081:CCAAT-Binding Factor / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation / Q000502:physiology; D004257:DNA Polymerase II / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D016193:G1 Phase / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D020868:Gene Silencing; D019942:Genes, p16 / Q000502:physiology; D006360:Heat-Shock Proteins / Q000235:genetics; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D008745:Methylation; D008938:Mitosis / Q000235:genetics*; D008957:Models, Genetic; D009707:Nucleosomes / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016192:Resting Phase, Cell Cycle / Q000235:genetics; D017422:Sequence Analysis, DNA; D035181:TATA-Box Binding Protein / Q000378:metabolism; D024363:Transcription Initiation Site / Q000502:physiology; D000097869:Polo-Like Kinase 1
D023081:CCAAT-Binding Factor; D018797:Cell Cycle Proteins; D004257:DNA Polymerase II; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D006657:Histones; D008565:Membrane Proteins; D009707:Nucleosomes; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D035181:TATA-Box Binding Protein; D000097869:Polo-Like Kinase 1; C000717247:HSPA5 protein, human; C509817:TBP protein, human; C077020:histone H2A.F-Z; C114987:wolframin protein