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PMID: 23407553 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Validation Study

Quantitative genetic-interaction mapping in mammalian cells.

Nature methods ·Vol. 10 ·No. 5 ·2013-05-00 ·Pages 432-7

Roguev A, Talbot D, Negri GL, Shales M, Cagney G, Bandyopadhyay S, Panning B, Krogan NJ

Abstract

Mapping genetic interactions (GIs) by simultaneously perturbing pairs of genes is a powerful tool for understanding complex biological phenomena. Here we describe an experimental platform for generating quantitative GI maps in mammalian cells using a combinatorial RNA interference strategy. We performed ∼11,000 pairwise knockdowns in mouse fibroblasts, focusing on 130 factors involved in chromatin regulation to create a GI map. Comparison of the GI and protein-protein interaction (PPI) data revealed that pairs of genes exhibiting positive GIs and/or similar genetic profiles were predictive of the corresponding proteins being physically associated. The mammalian GI map identified pathways and complexes but also resolved functionally distinct submodules within larger protein complexes. By integrating GI and PPI data, we created a functional map of chromatin complexes in mouse fibroblasts, revealing that the PAF complex is a central player in the mammalian chromatin landscape.

MeSH Terms
Animals Chromatin/metabolism Epistasis, Genetic Gene Knockdown Techniques Mice RNA Interference
Chemicals
Chromatin
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Roguev Assen
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA.
Talbot Dale
Negri Gian Luca
Shales Michael
Cagney Gerard
Bandyopadhyay Sourav
Panning Barbara
Krogan Nevan J
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Article Info
Journal
Nature methods
Abbr.
Nat Methods
ISSN
1548-7105
DOI
10.1038/nmeth.2398
Published
2013-05-00
Epub
2013-00-13
Pages
432-7
Language
English
Region
United States
NLM ID
101215604
PMCID
PMC3641890
Subset
IM
Grants
NIGMS NIH HHS · GM082250 · United States
NIGMS NIH HHS · GM081879 · United States
NIGMS NIH HHS · R01 GM085186 · United States
NIGMS NIH HHS · P50 GM081879 · United States
NIGMS NIH HHS · GM085186 · United States
NCI NIH HHS · P50CA58207 · United States
NIGMS NIH HHS · P50 GM082250 · United States
NIAID NIH HHS · P30 AI027763 · United States
NIAID NIH HHS · AI091575 · United States
NIAID NIH HHS · P01 AI091575 · United States
NIAID NIH HHS · P01 AI090935 · United States
NIAID NIH HHS · AI090935 · United States
NCI NIH HHS · P50 CA058207 · United States
Corrections
CommentIn
PMID: 23629415
CommentIn
PMID: 23653921
External Links
PubMed source DOI: 10.1038/nmeth.2398 PMC Full Text View journal details
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