title: Gene bookmarking accelerates the kinetics of post-mitotic transcriptional re-activation.
abstract: Although transmission of the gene expression program from mother to daughter cells has been suggested to be mediated by gene bookmarking, the precise mechanism by which bookmarking mediates post-mitotic transcriptional re-activation has been unclear. Here, we used a real-time gene expression system to quantitatively demonstrate that transcriptional activation of the same genetic locus occurs with a significantly more rapid kinetics in post-mitotic cells versus interphase cells. RNA polymerase II large subunit (Pol II) and bromodomain protein 4 (BRD4) were recruited to the locus in a different sequential order on interphase initiation versus post-mitotic re-activation resulting from the recognition by BRD4 of increased levels of histone H4 Lys 5 acetylation (H4K5ac) on the previously activated locus. BRD4 accelerated the dynamics of messenger RNA synthesis by de-compacting chromatin and hence facilitating transcriptional re-activation. Using a real-time quantitative approach, we identified differences in the kinetics of transcriptional activation between interphase and post-mitotic cells that are mediated by a chromatin-based epigenetic mechanism.
authors: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
authors: Rui
authors: R
authors: Zhao
authors: Tetsuya
authors: T
authors: Nakamura
authors: Yu
authors: Y
authors: Fu
authors: Zsolt
authors: Z
authors: Lazar
authors: David L
authors: DL
authors: Spector
mesh_terms: D000107:Acetylation; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007399:Interphase / Q000235:genetics*; D007700:Kinetics; D008239:Lysine; D008938:Mitosis / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D000092468:Bromodomain Containing Proteins
chemical_list: D018797:Cell Cycle Proteins; D006657:Histones; D008239:Lysine; D009687:Nuclear Proteins; D012319:RNA Polymerase II; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins