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.
Harukazu
H
Suzuki
Alistair R R
AR
Forrest
Erik
E
van Nimwegen
Carsten O
CO
Daub
Piotr J
PJ
Balwierz
Katharine M
KM
Irvine
Timo
T
Lassmann
Timothy
T
Ravasi
Yuki
Y
Hasegawa
Michiel J L
MJ
de Hoon
Shintaro
S
Katayama
Kate
K
Schroder
Piero
P
Carninci
Yasuhiro
Y
Tomaru
Mutsumi
M
Kanamori-Katayama
Atsutaka
A
Kubosaki
Altuna
A
Akalin
Yoshinari
Y
Ando
Erik
E
Arner
Maki
M
Asada
Hiroshi
H
Asahara
Timothy
T
Bailey
Vladimir B
VB
Bajic
Denis
D
Bauer
Anthony G
AG
Beckhouse
Nicolas
N
Bertin
Johan
J
Björkegren
Frank
F
Brombacher
Erika
E
Bulger
Alistair M
AM
Chalk
Joe
J
Chiba
Nicole
N
Cloonan
Adam
A
Dawe
Josee
J
Dostie
Pär G
PG
Engström
Magbubah
M
Essack
Geoffrey J
GJ
Faulkner
J Lynn
JL
Fink
David
D
Fredman
Ko
K
Fujimori
Masaaki
M
Furuno
Takashi
T
Gojobori
Julian
J
Gough
Sean M
SM
Grimmond
Mika
M
Gustafsson
Megumi
M
Hashimoto
Takehiro
T
Hashimoto
Mariko
M
Hatakeyama
Susanne
S
Heinzel
Winston
W
Hide
Oliver
O
Hofmann
Michael
M
Hörnquist
Lukasz
L
Huminiecki
Kazuho
K
Ikeo
Naoko
N
Imamoto
Satoshi
S
Inoue
Yusuke
Y
Inoue
Ryoko
R
Ishihara
Takao
T
Iwayanagi
Anders
A
Jacobsen
Mandeep
M
Kaur
Hideya
H
Kawaji
Markus C
MC
Kerr
Ryuichiro
R
Kimura
Syuhei
S
Kimura
Yasumasa
Y
Kimura
Hiroaki
H
Kitano
Hisashi
H
Koga
Toshio
T
Kojima
Shinji
S
Kondo
Takeshi
T
Konno
Anders
A
Krogh
Adele
A
Kruger
Ajit
A
Kumar
Boris
B
Lenhard
Andreas
A
Lennartsson
Morten
M
Lindow
Marina
M
Lizio
Cameron
C
Macpherson
Norihiro
N
Maeda
Christopher A
CA
Maher
Monique
M
Maqungo
Jessica
J
Mar
Nicholas A
NA
Matigian
Hideo
H
Matsuda
John S
JS
Mattick
Stuart
S
Meier
Sei
S
Miyamoto
Etsuko
E
Miyamoto-Sato
Kazuhiko
K
Nakabayashi
Yutaka
Y
Nakachi
Mika
M
Nakano
Sanne
S
Nygaard
Toshitsugu
T
Okayama
Yasushi
Y
Okazaki
Haruka
H
Okuda-Yabukami
Valerio
V
Orlando
Jun
J
Otomo
Mikhail
M
Pachkov
Nikolai
N
Petrovsky
Charles
C
Plessy
John
J
Quackenbush
Aleksandar
A
Radovanovic
Michael
M
Rehli
Rintaro
R
Saito
Albin
A
Sandelin
Sebastian
S
Schmeier
Christian
C
Schönbach
Ariel S
AS
Schwartz
Colin A
CA
Semple
Miho
M
Sera
Jessica
J
Severin
Katsuhiko
K
Shirahige
Cas
C
Simons
George
G
St Laurent
Masanori
M
Suzuki
Takahiro
T
Suzuki
Matthew J
MJ
Sweet
Ryan J
RJ
Taft
Shizu
S
Takeda
Yoichi
Y
Takenaka
Kai
K
Tan
Martin S
MS
Taylor
Rohan D
RD
Teasdale
Jesper
J
Tegnér
Sarah
S
Teichmann
Eivind
E
Valen
Claes
C
Wahlestedt
Kazunori
K
Waki
Andrew
A
Waterhouse
Christine A
CA
Wells
Ole
O
Winther
Linda
L
Wu
Kazumi
K
Yamaguchi
Hiroshi
H
Yanagawa
Jun
J
Yasuda
Mihaela
M
Zavolan
David A
DA
Hume
Takahiro
T
Arakawa
Shiro
S
Fukuda
Kengo
K
Imamura
Chikatoshi
C
Kai
Ai
A
Kaiho
Tsugumi
T
Kawashima
Chika
C
Kawazu
Yayoi
Y
Kitazume
Miki
M
Kojima
Hisashi
H
Miura
Kayoko
K
Murakami
Mitsuyoshi
M
Murata
Noriko
N
Ninomiya
Hiromi
H
Nishiyori
Shohei
S
Noma
Chihiro
C
Ogawa
Takuma
T
Sano
Christophe
C
Simon
Michihira
M
Tagami
Yukari
Y
Takahashi
Jun
J
Kawai
Yoshihide
Y
Hayashizaki
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