Pausing of RNA Polymerase II Disrupts DNA-Specified Nucleosome Organization to Enable Precise Gene Regulation

被引:326
作者
Gilchrist, Daniel A. [1 ]
Dos Santos, Gilberto [1 ]
Fargo, David C. [2 ]
Xie, Bin [5 ]
Gao, Yuan [4 ,5 ]
Li, Leping [3 ]
Adelman, Karen [1 ]
机构
[1] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA
[2] NIEHS, Lib Informat Serv, NIH, Res Triangle Pk, NC 27709 USA
[3] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA
[4] Johns Hopkins Univ, Inst Cell Engn, Neurogenerat & Stem Cell Biol Program, Baltimore, MD 21205 USA
[5] Johns Hopkins Univ, Lieber Inst Brain Dev, Div Genom Epigenom & Bioinformat, Baltimore, MD 21205 USA
关键词
DROSOPHILA-MELANOGASTER; PROMOTER ARCHITECTURE; GAGA FACTOR; POL-II; P-TEFB; TRANSCRIPTION; ELONGATION; CHROMATIN; BINDING; NELF;
D O I
10.1016/j.cell.2010.10.004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Metazoan transcription is controlled through either coordinated recruitment of transcription machinery to the gene promoter or regulated pausing of RNA polymerase II (Pol II) in early elongation. We report that a striking difference between genes that use these distinct regulatory strategies lies in the "default" chromatin architecture specified by their DNA sequences. Pol II pausing is prominent at highly regulated genes whose sequences inherently disfavor nucleosome formation within the gene but favor occlusion of the promoter by nucleosomes. In contrast, housekeeping genes that lack pronounced Pol II pausing show higher nucleosome occupancy downstream, but their promoters are deprived of nucleosomes regardless of polymerase binding. Our results indicate that a key role of paused Pol II is to compete with nucleosomes for occupancy of highly regulated promoters, thereby preventing the formation of repressive chromatin architecture
引用
收藏
页码:540 / 551
页数:12
相关论文
共 42 条
[21]   Genome-scale profiling of histone H3.3 replacement patterns [J].
Mito, Y ;
Henikoff, JG ;
Henikoff, S .
NATURE GENETICS, 2005, 37 (10) :1090-1097
[22]   RNA polymerase is poised for activation across the genome [J].
Muse, Ginger W. ;
Gilchrist, Daniel A. ;
Nechaev, Sergei ;
Shah, Ruchir ;
Parker, Joel S. ;
Grissom, Sherry F. ;
Zeitlinger, Julia ;
Adelman, Karen .
NATURE GENETICS, 2007, 39 (12) :1507-1511
[23]   Global Analysis of Short RNAs Reveals Widespread Promoter-Proximal Stalling and Arrest of Pol II in Drosophila [J].
Nechaev, Sergei ;
Fargo, David C. ;
dos Santos, Gilberto ;
Liu, Liwen ;
Gao, Yuan ;
Adelman, Karen .
SCIENCE, 2010, 327 (5963) :335-338
[24]   High-throughput mapping of the chromatin structure of human promoters [J].
Ozsolak, Fatih ;
Song, Jun S. ;
Liu, X. Shirley ;
Fisher, David E. .
NATURE BIOTECHNOLOGY, 2007, 25 (02) :244-248
[25]   Controlling the elongation phase of transcription with P-TEFb [J].
Peterlin, B. Matija ;
Price, David H. .
MOLECULAR CELL, 2006, 23 (03) :297-305
[26]   c-Myc Regulates Transcriptional Pause Release [J].
Rahl, Peter B. ;
Lin, Charles Y. ;
Seila, Amy C. ;
Flynn, Ryan A. ;
McCuine, Scott ;
Burge, Christopher B. ;
Sharp, Phillip A. ;
Young, Richard A. .
CELL, 2010, 141 (03) :432-445
[27]   Transcriptional regulation and the role of diverse coactivators in animal cells [J].
Roeder, RG .
FEBS LETTERS, 2005, 579 (04) :909-915
[28]   THE RNA POLYMERASE-II MOLECULE AT THE 5' END OF THE UNINDUCED HSP70 GENE OF DROSOPHILA-MELANOGASTER IS TRANSCRIPTIONALLY ENGAGED [J].
ROUGVIE, AE ;
LIS, JT .
CELL, 1988, 54 (06) :795-804
[29]   Dynamic regulation of nucleosome positioning in the human genome [J].
Schones, Dustin E. ;
Cui, Kairong ;
Cuddapah, Suresh ;
Roh, Tae-Young ;
Barski, Artem ;
Wang, Zhibin ;
Wei, Gang ;
Zhao, Keji .
CELL, 2008, 132 (05) :887-898
[30]   Chromatin organization marks exon-intron structure [J].
Schwartz, Schraga ;
Meshorer, Eran ;
Ast, Gil .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2009, 16 (09) :990-U117