The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line.
Using deep sequencing (deepCAGE), the FANTOM4 study measured the genome-wide dynamics of transcription-start-site usage in the human monocytic cell line THP-1 throughout a time course of growth arrest and differentiation. Modeling the expression dynamics in terms of predicted cis-regulatory sites, we identified the key transcription regulators, their time-dependent activities and target genes. Systematic siRNA knockdown of 52 transcription factors confirmed the roles of individual factors in the regulatory network. Our results indicate that cellular states are constrained by complex networks involving both positive and negative regulatory interactions among substantial numbers of transcription factors and that no single transcription factor is both necessary and sufficient to drive the differentiation process.
RIKEN Omics Science Center, RIKEN Yokohama Institute, Kanagawa, Japan.
Suzuki
Harukazu
H
Forrest
Alistair R R
AR
van Nimwegen
Erik
E
Daub
Carsten O
CO
Balwierz
Piotr J
PJ
Irvine
Katharine M
KM
Lassmann
Timo
T
Ravasi
Timothy
T
Hasegawa
Yuki
Y
de Hoon
Michiel J L
MJ
Katayama
Shintaro
S
Schroder
Kate
K
Carninci
Piero
P
Tomaru
Yasuhiro
Y
Kanamori-Katayama
Mutsumi
M
Kubosaki
Atsutaka
A
Akalin
Altuna
A
Ando
Yoshinari
Y
Arner
Erik
E
Asada
Maki
M
Asahara
Hiroshi
H
Bailey
Timothy
T
Bajic
Vladimir B
VB
Bauer
Denis
D
Beckhouse
Anthony G
AG
Bertin
Nicolas
N
Björkegren
Johan
J
Brombacher
Frank
F
Bulger
Erika
E
Chalk
Alistair M
AM
Chiba
Joe
J
Cloonan
Nicole
N
Dawe
Adam
A
Dostie
Josee
J
Engström
Pär G
PG
Essack
Magbubah
M
Faulkner
Geoffrey J
GJ
Fink
J Lynn
JL
Fredman
David
D
Fujimori
Ko
K
Furuno
Masaaki
M
Gojobori
Takashi
T
Gough
Julian
J
Grimmond
Sean M
SM
Gustafsson
Mika
M
Hashimoto
Megumi
M
Hashimoto
Takehiro
T
Hatakeyama
Mariko
M
Heinzel
Susanne
S
Hide
Winston
W
Hofmann
Oliver
O
Hörnquist
Michael
M
Huminiecki
Lukasz
L
Ikeo
Kazuho
K
Imamoto
Naoko
N
Inoue
Satoshi
S
Inoue
Yusuke
Y
Ishihara
Ryoko
R
Iwayanagi
Takao
T
Jacobsen
Anders
A
Kaur
Mandeep
M
Kawaji
Hideya
H
Kerr
Markus C
MC
Kimura
Ryuichiro
R
Kimura
Syuhei
S
Kimura
Yasumasa
Y
Kitano
Hiroaki
H
Koga
Hisashi
H
Kojima
Toshio
T
Kondo
Shinji
S
Konno
Takeshi
T
Krogh
Anders
A
Kruger
Adele
A
Kumar
Ajit
A
Lenhard
Boris
B
Lennartsson
Andreas
A
Lindow
Morten
M
Lizio
Marina
M
Macpherson
Cameron
C
Maeda
Norihiro
N
Maher
Christopher A
CA
Maqungo
Monique
M
Mar
Jessica
J
Matigian
Nicholas A
NA
Matsuda
Hideo
H
Mattick
John S
JS
Meier
Stuart
S
Miyamoto
Sei
S
Miyamoto-Sato
Etsuko
E
Nakabayashi
Kazuhiko
K
Nakachi
Yutaka
Y
Nakano
Mika
M
Nygaard
Sanne
S
Okayama
Toshitsugu
T
Okazaki
Yasushi
Y
Okuda-Yabukami
Haruka
H
Orlando
Valerio
V
Otomo
Jun
J
Pachkov
Mikhail
M
Petrovsky
Nikolai
N
Plessy
Charles
C
Quackenbush
John
J
Radovanovic
Aleksandar
A
Rehli
Michael
M
Saito
Rintaro
R
Sandelin
Albin
A
Schmeier
Sebastian
S
Schönbach
Christian
C
Schwartz
Ariel S
AS
Semple
Colin A
CA
Sera
Miho
M
Severin
Jessica
J
Shirahige
Katsuhiko
K
Simons
Cas
C
St Laurent
George
G
Suzuki
Masanori
M
Suzuki
Takahiro
T
Sweet
Matthew J
MJ
Taft
Ryan J
RJ
Takeda
Shizu
S
Takenaka
Yoichi
Y
Tan
Kai
K
Taylor
Martin S
MS
Teasdale
Rohan D
RD
Tegnér
Jesper
J
Teichmann
Sarah
S
Valen
Eivind
E
Wahlestedt
Claes
C
Waki
Kazunori
K
Waterhouse
Andrew
A
Wells
Christine A
CA
Winther
Ole
O
Wu
Linda
L
Yamaguchi
Kazumi
K
Yanagawa
Hiroshi
H
Yasuda
Jun
J
Zavolan
Mihaela
M
Hume
David A
DA
Arakawa
Takahiro
T
Fukuda
Shiro
S
Imamura
Kengo
K
Kai
Chikatoshi
C
Kaiho
Ai
A
Kawashima
Tsugumi
T
Kawazu
Chika
C
Kitazume
Yayoi
Y
Kojima
Miki
M
Miura
Hisashi
H
Murakami
Kayoko
K
Murata
Mitsuyoshi
M
Ninomiya
Noriko
N
Nishiyori
Hiromi
H
Noma
Shohei
S
Ogawa
Chihiro
C
Sano
Takuma
T
Simon
Christophe
C
Tagami
Michihira
M
Takahashi
Yukari
Y
Kawai
Jun
J
Hayashizaki
Yoshihide
Y
D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000378:metabolism; D014158:Transcription, Genetic
D034741:RNA, Small Interfering