Discovery of Novel Human Gene Regulatory Modules from Gene Co-expression and Promoter Motif Analysis

Abstract Deciphering gene regulatory networks requires identification of gene expression modules. We describe a novel bottom-up approach to identify gene modules regulated by cis-regulatory motifs from a human gene co-expression network. Target genes of a cis-regulatory motif were identified from th...

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Autores principales:	Shisong Ma, Michael Snyder, Savithramma P. Dinesh-Kumar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/28d98b6695fd4ff6827580ddae4e90a9
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spelling	oai:doaj.org-article:28d98b6695fd4ff6827580ddae4e90a92021-12-02T15:05:48ZDiscovery of Novel Human Gene Regulatory Modules from Gene Co-expression and Promoter Motif Analysis10.1038/s41598-017-05705-22045-2322https://doaj.org/article/28d98b6695fd4ff6827580ddae4e90a92017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05705-2https://doaj.org/toc/2045-2322Abstract Deciphering gene regulatory networks requires identification of gene expression modules. We describe a novel bottom-up approach to identify gene modules regulated by cis-regulatory motifs from a human gene co-expression network. Target genes of a cis-regulatory motif were identified from the network via the motif’s enrichment or biased distribution towards transcription start sites in the promoters of co-expressed genes. A gene sub-network containing the target genes was extracted and used to derive gene modules. The analysis revealed known and novel gene modules regulated by the NF-Y motif. The binding of NF-Y proteins to these modules’ gene promoters were verified using ENCODE ChIP-Seq data. The analyses also identified 8,048 Sp1 motif target genes, interestingly many of which were not detected by ENCODE ChIP-Seq. These target genes assemble into house-keeping, tissues-specific developmental, and immune response modules. Integration of Sp1 modules with genomic and epigenomic data indicates epigenetic control of Sp1 targets’ expression in a cell/tissue specific manner. Finally, known and novel target genes and modules regulated by the YY1, RFX1, IRF1, and 34 other motifs were also identified. The study described here provides a valuable resource to understand transcriptional regulation of various human developmental, disease, or immunity pathways.Shisong MaMichael SnyderSavithramma P. Dinesh-KumarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shisong Ma Michael Snyder Savithramma P. Dinesh-Kumar Discovery of Novel Human Gene Regulatory Modules from Gene Co-expression and Promoter Motif Analysis
description	Abstract Deciphering gene regulatory networks requires identification of gene expression modules. We describe a novel bottom-up approach to identify gene modules regulated by cis-regulatory motifs from a human gene co-expression network. Target genes of a cis-regulatory motif were identified from the network via the motif’s enrichment or biased distribution towards transcription start sites in the promoters of co-expressed genes. A gene sub-network containing the target genes was extracted and used to derive gene modules. The analysis revealed known and novel gene modules regulated by the NF-Y motif. The binding of NF-Y proteins to these modules’ gene promoters were verified using ENCODE ChIP-Seq data. The analyses also identified 8,048 Sp1 motif target genes, interestingly many of which were not detected by ENCODE ChIP-Seq. These target genes assemble into house-keeping, tissues-specific developmental, and immune response modules. Integration of Sp1 modules with genomic and epigenomic data indicates epigenetic control of Sp1 targets’ expression in a cell/tissue specific manner. Finally, known and novel target genes and modules regulated by the YY1, RFX1, IRF1, and 34 other motifs were also identified. The study described here provides a valuable resource to understand transcriptional regulation of various human developmental, disease, or immunity pathways.
format	article
author	Shisong Ma Michael Snyder Savithramma P. Dinesh-Kumar
author_facet	Shisong Ma Michael Snyder Savithramma P. Dinesh-Kumar
author_sort	Shisong Ma
title	Discovery of Novel Human Gene Regulatory Modules from Gene Co-expression and Promoter Motif Analysis
title_short	Discovery of Novel Human Gene Regulatory Modules from Gene Co-expression and Promoter Motif Analysis
title_full	Discovery of Novel Human Gene Regulatory Modules from Gene Co-expression and Promoter Motif Analysis
title_fullStr	Discovery of Novel Human Gene Regulatory Modules from Gene Co-expression and Promoter Motif Analysis
title_full_unstemmed	Discovery of Novel Human Gene Regulatory Modules from Gene Co-expression and Promoter Motif Analysis
title_sort	discovery of novel human gene regulatory modules from gene co-expression and promoter motif analysis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/28d98b6695fd4ff6827580ddae4e90a9
work_keys_str_mv	AT shisongma discoveryofnovelhumangeneregulatorymodulesfromgenecoexpressionandpromotermotifanalysis AT michaelsnyder discoveryofnovelhumangeneregulatorymodulesfromgenecoexpressionandpromotermotifanalysis AT savithrammapdineshkumar discoveryofnovelhumangeneregulatorymodulesfromgenecoexpressionandpromotermotifanalysis
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Discovery of Novel Human Gene Regulatory Modules from Gene Co-expression and Promoter Motif Analysis

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