The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line

Harukazu Suzuki; Alistair R R Forrest; Erik van Nimwegen; Carsten O Daub; Piotr J Balwierz; Katharine M Irvine; Timo Lassmann; Timothy Ravasi; Yuki Hasegawa; Michiel J L de Hoon; Shintaro Katayama; Kate Schroder; Piero Carninci; Yasuhiro Tomaru; Mutsumi Kanamori-Katayama; Atsutaka Kubosaki; Altuna Akalin; Yoshinari Ando; Erik Arner; Maki Asada; Hiroshi Asahara; Timothy Bailey; Vladimir B Bajic; Denis Bauer; Anthony G Beckhouse; Nicolas Bertin; Johan Björkegren; Frank Brombacher; Erika Bulger; Alistair M Chalk; Joe Chiba; Nicole Cloonan; Adam Dawe; Josee Dostie; Pär G Engström; Magbubah Essack; Geoffrey J Faulkner; J Lynn Fink; David Fredman; Ko Fujimori; Masaaki Furuno; Takashi Gojobori; Julian Gough; Sean M Grimmond; Anders Jacobsen; Anders Krogh; Sanne Nygaard; Albin Sandelin; Eivind Valen; Ole Winther; Riken Omics Science Center

doi:10.1038/ng.375

The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line

Harukazu Suzuki, Alistair R R Forrest, Erik van Nimwegen, Carsten O Daub, Piotr J Balwierz, Katharine M Irvine, Timo Lassmann, Timothy Ravasi, Yuki Hasegawa, Michiel J L de Hoon, Shintaro Katayama, Kate Schroder, Piero Carninci, Yasuhiro Tomaru, Mutsumi Kanamori-Katayama, Atsutaka Kubosaki, Altuna Akalin, Yoshinari Ando, Erik Arner, Maki AsadaHiroshi Asahara, Timothy Bailey, Vladimir B Bajic, Denis Bauer, Anthony G Beckhouse, Nicolas Bertin, Johan Björkegren, Frank Brombacher, Erika Bulger, Alistair M Chalk, Joe Chiba, Nicole Cloonan, Adam Dawe, Josee Dostie, Pär G Engström, Magbubah Essack, Geoffrey J Faulkner, J Lynn Fink, David Fredman, Ko Fujimori, Masaaki Furuno, Takashi Gojobori, Julian Gough, Sean M Grimmond, Anders Jacobsen, Anders Krogh, Sanne Nygaard, Albin Sandelin, Eivind Valen, Ole Winther, Riken Omics Science Center

325 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Nature Genetics
Volume	41
Issue number	5
Pages (from-to)	553-62
Number of pages	9
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.375
Publication status	Published - 2009

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Suzuki, H., Forrest, A. R. R., van Nimwegen, E., Daub, C. O., Balwierz, P. J., Irvine, K. M., Lassmann, T., Ravasi, T., Hasegawa, Y., de Hoon, M. J. L., Katayama, S., Schroder, K., Carninci, P., Tomaru, Y., Kanamori-Katayama, M., Kubosaki, A., Akalin, A., Ando, Y., Arner, E., ... Riken Omics Science Center (2009). The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line. Nature Genetics, 41(5), 553-62. https://doi.org/10.1038/ng.375

Suzuki, H, Forrest, ARR, van Nimwegen, E, Daub, CO, Balwierz, PJ, Irvine, KM, Lassmann, T, Ravasi, T, Hasegawa, Y, de Hoon, MJL, Katayama, S, Schroder, K, Carninci, P, Tomaru, Y, Kanamori-Katayama, M, Kubosaki, A, Akalin, A, Ando, Y, Arner, E, Asada, M, Asahara, H, Bailey, T, Bajic, VB, Bauer, D, Beckhouse, AG, Bertin, N, Björkegren, J, Brombacher, F, Bulger, E, Chalk, AM, Chiba, J, Cloonan, N, Dawe, A, Dostie, J, Engström, PG, Essack, M, Faulkner, GJ, Fink, JL, Fredman, D, Fujimori, K, Furuno, M, Gojobori, T, Gough, J, Grimmond, SM, Jacobsen, A, Krogh, A, Nygaard, S, Sandelin, A, Valen, E, Winther, O & Riken Omics Science Center 2009, 'The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line', Nature Genetics, vol. 41, no. 5, pp. 553-62. https://doi.org/10.1038/ng.375

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title = "The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line",

abstract = "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.",

author = "Harukazu Suzuki and Forrest, {Alistair R R} and {van Nimwegen}, Erik and Daub, {Carsten O} and Balwierz, {Piotr J} and Irvine, {Katharine M} and Timo Lassmann and Timothy Ravasi and Yuki Hasegawa and {de Hoon}, {Michiel J L} and Shintaro Katayama and Kate Schroder and Piero Carninci and Yasuhiro Tomaru and Mutsumi Kanamori-Katayama and Atsutaka Kubosaki and Altuna Akalin and Yoshinari Ando and Erik Arner and Maki Asada and Hiroshi Asahara and Timothy Bailey and Bajic, {Vladimir B} and Denis Bauer and Beckhouse, {Anthony G} and Nicolas Bertin and Johan Bj{\"o}rkegren and Frank Brombacher and Erika Bulger and Chalk, {Alistair M} and Joe Chiba and Nicole Cloonan and Adam Dawe and Josee Dostie and Engstr{\"o}m, {P{\"a}r G} and Magbubah Essack and Faulkner, {Geoffrey J} and Fink, {J Lynn} and David Fredman and Ko Fujimori and Masaaki Furuno and Takashi Gojobori and Julian Gough and Grimmond, {Sean M} and Anders Jacobsen and Anders Krogh and Sanne Nygaard and Albin Sandelin and Eivind Valen and Ole Winther and {Riken Omics Science Center}",

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AU - Suzuki, Harukazu

AU - Forrest, Alistair R R

AU - van Nimwegen, Erik

AU - Daub, Carsten O

AU - Balwierz, Piotr J

AU - Irvine, Katharine M

AU - Lassmann, Timo

AU - Ravasi, Timothy

AU - Hasegawa, Yuki

AU - de Hoon, Michiel J L

AU - Katayama, Shintaro

AU - Schroder, Kate

AU - Carninci, Piero

AU - Tomaru, Yasuhiro

AU - Kanamori-Katayama, Mutsumi

AU - Kubosaki, Atsutaka

AU - Akalin, Altuna

AU - Ando, Yoshinari

AU - Arner, Erik

AU - Asada, Maki

AU - Asahara, Hiroshi

AU - Bailey, Timothy

AU - Bajic, Vladimir B

AU - Bauer, Denis

AU - Beckhouse, Anthony G

AU - Bertin, Nicolas

AU - Björkegren, Johan

AU - Brombacher, Frank

AU - Bulger, Erika

AU - Chalk, Alistair M

AU - Chiba, Joe

AU - Cloonan, Nicole

AU - Dawe, Adam

AU - Dostie, Josee

AU - Engström, Pär G

AU - Essack, Magbubah

AU - Faulkner, Geoffrey J

AU - Fink, J Lynn

AU - Fredman, David

AU - Fujimori, Ko

AU - Furuno, Masaaki

AU - Gojobori, Takashi

AU - Gough, Julian

AU - Grimmond, Sean M

AU - Jacobsen, Anders

AU - Krogh, Anders

AU - Nygaard, Sanne

AU - Sandelin, Albin

AU - Valen, Eivind

AU - Winther, Ole

AU - Riken Omics Science Center

PY - 2009

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N2 - 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.

AB - 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.

U2 - 10.1038/ng.375

DO - 10.1038/ng.375

M3 - Journal article

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SN - 1061-4036

VL - 41

SP - 553

EP - 562

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line

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