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 Margolin, Ulf Klein, Riccardo Dalla-Favera, Andrea Califano

Research output: Contribution to journalArticle

158 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Transcription factors
Human Activities
Modulators
B-Lymphocytes
Transcription Factors
Genes
Cells
Genome
Proteins
Epigenomics
Lymphocytes
Transcription
Enzymes
Throughput
Modulation

ASJC Scopus subject areas

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

Cite this

Wang, K., Saito, M., Bisikirska, B. C., Alvarez, M. J., Lim, W. K., Rajbhandari, P., ... Califano, A. (2009). Genome-wide identification of post-translational modulators of transcription factor activity in human B cells. Nature Biotechnology, 27(9), 829-837. https://doi.org/10.1038/nbt.1563

Genome-wide identification of post-translational modulators of transcription factor activity in human B cells. / Wang, Kai; Saito, Masumichi; Bisikirska, Brygida C.; Alvarez, Mariano J.; Lim, Wei Keat; Rajbhandari, Presha; Shen, Qiong; Nemenman, Ilya; Basso, Katia; Margolin, Adam; Klein, Ulf; Dalla-Favera, Riccardo; Califano, Andrea.

In: Nature Biotechnology, Vol. 27, No. 9, 09.2009, p. 829-837.

Research output: Contribution to journalArticle

Wang, K, Saito, M, Bisikirska, BC, Alvarez, MJ, Lim, WK, Rajbhandari, P, Shen, Q, Nemenman, I, Basso, K, Margolin, A, Klein, U, Dalla-Favera, R & Califano, A 2009, 'Genome-wide identification of post-translational modulators of transcription factor activity in human B cells', Nature Biotechnology, vol. 27, no. 9, pp. 829-837. https://doi.org/10.1038/nbt.1563
Wang, Kai ; Saito, Masumichi ; Bisikirska, Brygida C. ; Alvarez, Mariano J. ; Lim, Wei Keat ; Rajbhandari, Presha ; Shen, Qiong ; Nemenman, Ilya ; Basso, Katia ; Margolin, Adam ; Klein, Ulf ; Dalla-Favera, Riccardo ; Califano, Andrea. / Genome-wide identification of post-translational modulators of transcription factor activity in human B cells. In: Nature Biotechnology. 2009 ; Vol. 27, No. 9. pp. 829-837.
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