A wave of nascent transcription on activated human genes.
Genome-wide studies reveal that transcription by RNA polymerase II (Pol II) is dynamically regulated. To obtain a comprehensive view of a single transcription cycle, we switched on transcription of five long human genes (>100 kbp) with tumor necrosis factor-alpha (TNFalpha) and monitored (using microarrays, RNA fluorescence in situ hybridization, and chromatin immunoprecipitation) the appearance of nascent RNA, changes in binding of Pol II and two insulators (the cohesin subunit RAD21 and the CCCTC-binding factor CTCF), and modifications of histone H3. Activation triggers a wave of transcription that sweeps along the genes at approximately 3.1 kbp/min; splicing occurs cotranscriptionally, a major checkpoint acts several kilobases downstream of the transcription start site to regulate polymerase transit, and Pol II tends to stall at cohesin/CTCF binding sites.
Wada
Youichiro
Y
Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
Ohta
Yoshihiro
Y
Xu
Meng
M
Tsutsumi
Shuichi
S
Minami
Takashi
T
Inoue
Kenji
K
Komura
Daisuke
D
Kitakami
Jun'ichi
J
Oshida
Nobuhiko
N
Papantonis
Argyris
A
Izumi
Akashi
A
Kobayashi
Mika
M
Meguro
Hiroko
H
Kanki
Yasuharu
Y
Mimura
Imari
I
Yamamoto
Kazuki
K
Mataki
Chikage
C
Hamakubo
Takao
T
Shirahige
Katsuhiko
K
Aburatani
Hiroyuki
H
Kimura
Hiroshi
H
Kodama
Tatsuhiko
T
Cook
Peter R
PR
Ihara
Sigeo
S
D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D006801:Humans; D017403:In Situ Hybridization; D007438:Introns; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D012326:RNA Splicing; D012333:RNA, Messenger / Q000096:biosynthesis; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D000097722:Cohesins
D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012319:RNA Polymerase II; D012333:RNA, Messenger; D012097:Repressor Proteins; D014409:Tumor Necrosis Factor-alpha; D000097722:Cohesins; C000619697:CTCF protein, human; C429022:RAD21 protein, human