Genome-wide identification of post-translational modulators of transcription factor activity in human B cells

Kai Wang, Masumichi Saito, Brygida C. Bisikirska, Mariano J. Alvarez, Wei Keat Lim, Presha Rajbhandari, Qiong Shen, Ilya Nemenman, Katia Basso, Adam A. Margolin, Ulf Klein, Riccardo Dalla-Favera, Andrea Califano

Research output: Contribution to journalArticlepeer-review

178 Scopus citations

Abstract

The ability of a transcription factor (TF) to regulate its targets is modulated by a variety of genetic and epigenetic mechanisms, resulting in highly context-dependent regulatory networks. However, high-throughput methods for the identification of proteins that affect TF activity are still largely unavailable. Here we introduce an algorithm, modulator inference by network dynamics (MINDy), for the genome-wide identification of post-translational modulators of TF activity within a specific cellular context. When used to dissect the regulation of MYC activity in human B lymphocytes, the approach inferred novel modulators of MYC function, which act by distinct mechanisms, including protein turnover, transcription complex formation and selective enzyme recruitment. MINDy is generally applicable to study the post-translational modulation of mammalian TFs in any cellular context. As such it can be used to dissect context-specific signaling pathways and combinatorial transcriptional regulation.

Original languageEnglish (US)
Pages (from-to)829-837
Number of pages9
JournalNature biotechnology
Volume27
Issue number9
DOIs
StatePublished - Sep 2009

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

Fingerprint Dive into the research topics of 'Genome-wide identification of post-translational modulators of transcription factor activity in human B cells'. Together they form a unique fingerprint.

Cite this