Regulatory module network of basic-helix-loop-helix transcription factors in mouse brainReport as inadecuate




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Genome Biology

, 8:R244

First Online: 19 November 2007Received: 18 June 2007Revised: 14 September 2007Accepted: 19 November 2007

Abstract

BackgroundThe basic-helix-loop-helix bHLH proteins are important components of the transcriptional regulatory network, controlling a variety of biological processes, especially the development of the central nervous system. Until now, reports describing the regulatory network of the bHLH transcription factor TF family have been scarce. In order to understand the regulatory mechanisms of bHLH TFs in mouse brain, we inferred their regulatory network from genome-wide gene expression profiles with the module networks method.

ResultsA regulatory network comprising 15 important bHLH TFs and 153 target genes was constructed. The network was divided into 28 modules based on expression profiles. A regulatory-motif search shows the complexity and diversity of the network. In addition, 26 cooperative bHLH TF pairs were also detected in the network. This cooperation suggests possible physical interactions or genetic regulation between TFs. Interestingly, some TFs in the network regulate more than one module. A novel cross-repression between Neurod6 and Hey2 was identified, which may control various functions in different brain regions. The presence of TF binding sites TFBSs in the promoter regions of their target genes validates more than 70% of TF-target gene pairs of the network. Literature mining provides additional support for five modules. More importantly, the regulatory relationships among selected key components are all validated in mutant mice.

ConclusionOur network is reliable and very informative for understanding the role of bHLH TFs in mouse brain development and function. It provides a framework for future experimental analyses.

AbbreviationsbHLHbasic-helix-loop-helix

BSbinding site

DBMDNA-binding motif

GOGene Ontology

MMmultiple module

TFtranscription factors

TFBSTF binding site.

Electronic supplementary materialThe online version of this article doi:10.1186-gb-2007-8-11-r244 contains supplementary material, which is available to authorized users.

Jing Li, Zijing J Liu contributed equally to this work.

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Author: Jing Li - Zijing J Liu - Yuchun C Pan - Qi Liu - Xing Fu - Nigel GF Cooper - Yixue Li - Mengsheng Qiu - Tieliu Shi

Source: https://link.springer.com/







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