The Transcriptional Network That Controls Growth Arrest and Differentiation in a Human Myeloid Leukemia Cell Line

Nat Genet. 2009 May;41(5):553-62. doi: 10.1038/ng.375. Epub 2009 Apr 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Differentiation / genetics*
  • Cell Line
  • Cell Proliferation*
  • Gene Expression Profiling
  • Gene Regulatory Networks*
  • Humans
  • Leukemia, Myeloid / genetics
  • Leukemia, Myeloid / metabolism
  • Models, Genetic
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic
  • RNA, Small Interfering / metabolism
  • Transcription, Genetic*

Substances

  • RNA, Small Interfering