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

Research output: Contribution to journalJournal articleResearchpeer-review

  • 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
  • Krogh, Anders
  • Sanne Nygaard
  • Sandelin, Albin Gustav
  • Eivind Valen
  • Winther, Ole
  • Riken Omics Science Center
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 languageEnglish
JournalNature Genetics
Issue number5
Pages (from-to)553-62
Number of pages9
Publication statusPublished - 2009

ID: 12866073