Journal
NATURE BIOTECHNOLOGY
Volume 27, Issue 9, Pages 829-U84Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt.1563
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Funding
- US National Cancer Institute [R01CA109755]
- National Institute of Allergy and Infectious Diseases [R01AI066116]
- National Centers for Biomedical Computing NIH Roadmap Initiative [U54CA121852]
- National Institute for General Medical Sciences [R21GM080216]
- IBM
- NATIONAL CANCER INSTITUTE [R01CA109755, U54CA121852] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI066116] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R21GM080216] Funding Source: NIH RePORTER
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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.
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