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Human gene-centered transcription factor networks for enhancers and disease variants.

ABSTRACT: Gene regulatory networks (GRNs) comprising interactions between transcription factors (TFs) and regulatory loci control development and physiology. Numerous disease-associated mutations have been identified, the vast majority residing in non-coding regions of the genome. As current GRN mapping methods test one TF at a time and require the use of cells harboring the mutation(s) of interest, they are not suitable to identify TFs that bind to wild-type and mutant loci. Here, we use gene-centered yeast one-hybrid (eY1H) assays to interrogate binding of 1,086 human TFs to 246 enhancers, as well as to 109 non-coding disease mutations. We detect both loss and gain of TF interactions with mutant loci that are concordant with target gene expression changes. This work establishes eY1H assays as a powerful addition to the toolkit of mapping human GRNs and for the high-throughput characterization of genomic variants that are rapidly being identified by genome-wide association studies.

SUBMITTER: Fuxman Bass JI

PROVIDER: S-EPMC4409666 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Human gene-centered transcription factor networks for enhancers and disease variants.

Fuxman Bass Juan I JI Sahni Nidhi N Shrestha Shaleen S Garcia-Gonzalez Aurian A Mori Akihiro A Bhat Numana N Yi Song S Hill David E DE Vidal Marc M Walhout Albertha J M AJM

Cell 20150401 3

Gene regulatory networks (GRNs) comprising interactions between transcription factors (TFs) and regulatory loci control development and physiology. Numerous disease-associated mutations have been identified, the vast majority residing in non-coding regions of the genome. As current GRN mapping methods test one TF at a time and require the use of cells harboring the mutation(s) of interest, they are not suitable to identify TFs that bind to wild-type and mutant loci. Here, we use gene-centered ye ...[more]

PMID: 25910213

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Human gene-centered transcription factor networks for enhancers and disease variants.

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Human gene-centered transcription factor networks for enhancers and disease variants.

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