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The logic of transcriptional regulator recruitment architecture at cis-regulatory modules controlling liver functions

Julie Dubois-Chevalier, Vanessa Dubois (UGent) , Helene Dehondt, Parisa Mazrooei, Claire Mazuy, Aurelien A. Serandour, Celine Gheeraert, Penderia Guillaume, Eric Bauge, Bruno Derudas, et al.
(2017) GENOME RESEARCH. 27(6). p.985-996
Author
Organization
Abstract
Control of gene transcription relies on concomitant regulation by multiple transcriptional regulators (TRs). However, how recruitment of a myriad of TRs is orchestrated at cis-regulatory modules (CRMs) to account for coregulation of specific biological pathways is only partially understood. Here, we have used mouse liver CRMs involved in regulatory activities of the hepatic TR, NR1H4 (FXR; farnesoid X receptor), as our model system to tackle this question. Using integrative cistromic, epigenomic, transcriptomic, and interactomic analyses, we reveal a logical organization where trans-regulatory modules (TRMs), which consist of subsets of preferentially and coordinately corecruited TRs, assemble into hierarchical combinations at hepatic CRMs. Different combinations of TRMs add to a core TRM, broadly found across the whole landscape of CRMs, to discriminate promoters from enhancers. These combinations also specify distinct sets of CRM differentially organized along the genome and involved in regulation of either housekeeping/cellular maintenance genes or liverspecific functions. In addition to these TRMs which we define as obligatory, we show that facultative TRMs, such as one comprising core circadian TRs, are further recruited to selective subsets of CRMs to modulate their activities. TRMs transcend TR classification into ubiquitous versus liver-identity factors, as well as TR grouping into functional families. Hence, hierarchical superimpositions of obligatory and facultative TRMs bring about independent transcriptional regulatory inputs defining different sets of CRMs with logical connection to regulation of specific gene sets and biological pathways. Altogether, our study reveals novel principles of concerted transcriptional regulation by multiple TRs at CRMs.
Keywords
ACTIVATED RECEPTOR-GAMMA, TOPOLOGICAL DOMAINS, ENRICHMENT ANALYSIS, GENE-TRANSCRIPTION, LIPID-METABOLISM, EXPRESSION, BINDING, FXR, ENHANCERS, ALPHA

Citation

Please use this url to cite or link to this publication:

MLA
Dubois-Chevalier, Julie, et al. “The Logic of Transcriptional Regulator Recruitment Architecture at Cis-Regulatory Modules Controlling Liver Functions.” GENOME RESEARCH, vol. 27, no. 6, 2017, pp. 985–96, doi:10.1101/gr.217075.116.
APA
Dubois-Chevalier, J., Dubois, V., Dehondt, H., Mazrooei, P., Mazuy, C., Serandour, A. A., … Eeckhoute, J. (2017). The logic of transcriptional regulator recruitment architecture at cis-regulatory modules controlling liver functions. GENOME RESEARCH, 27(6), 985–996. https://doi.org/10.1101/gr.217075.116
Chicago author-date
Dubois-Chevalier, Julie, Vanessa Dubois, Helene Dehondt, Parisa Mazrooei, Claire Mazuy, Aurelien A. Serandour, Celine Gheeraert, et al. 2017. “The Logic of Transcriptional Regulator Recruitment Architecture at Cis-Regulatory Modules Controlling Liver Functions.” GENOME RESEARCH 27 (6): 985–96. https://doi.org/10.1101/gr.217075.116.
Chicago author-date (all authors)
Dubois-Chevalier, Julie, Vanessa Dubois, Helene Dehondt, Parisa Mazrooei, Claire Mazuy, Aurelien A. Serandour, Celine Gheeraert, Penderia Guillaume, Eric Bauge, Bruno Derudas, Nathalie Hennuyer, Rejane Paumelle, Guillemette Marot, Jason S. Carroll, Mathieu Lupien, Bart Staels, Philippe Lefebvre, and Jerome Eeckhoute. 2017. “The Logic of Transcriptional Regulator Recruitment Architecture at Cis-Regulatory Modules Controlling Liver Functions.” GENOME RESEARCH 27 (6): 985–996. doi:10.1101/gr.217075.116.
Vancouver
1.
Dubois-Chevalier J, Dubois V, Dehondt H, Mazrooei P, Mazuy C, Serandour AA, et al. The logic of transcriptional regulator recruitment architecture at cis-regulatory modules controlling liver functions. GENOME RESEARCH. 2017;27(6):985–96.
IEEE
[1]
J. Dubois-Chevalier et al., “The logic of transcriptional regulator recruitment architecture at cis-regulatory modules controlling liver functions,” GENOME RESEARCH, vol. 27, no. 6, pp. 985–996, 2017.
@article{8737861,
  abstract     = {{Control of gene transcription relies on concomitant regulation by multiple transcriptional regulators (TRs). However, how recruitment of a myriad of TRs is orchestrated at cis-regulatory modules (CRMs) to account for coregulation of specific biological pathways is only partially understood. Here, we have used mouse liver CRMs involved in regulatory activities of the hepatic TR, NR1H4 (FXR; farnesoid X receptor), as our model system to tackle this question. Using integrative cistromic, epigenomic, transcriptomic, and interactomic analyses, we reveal a logical organization where trans-regulatory modules (TRMs), which consist of subsets of preferentially and coordinately corecruited TRs, assemble into hierarchical combinations at hepatic CRMs. Different combinations of TRMs add to a core TRM, broadly found across the whole landscape of CRMs, to discriminate promoters from enhancers. These combinations also specify distinct sets of CRM differentially organized along the genome and involved in regulation of either housekeeping/cellular maintenance genes or liverspecific functions. In addition to these TRMs which we define as obligatory, we show that facultative TRMs, such as one comprising core circadian TRs, are further recruited to selective subsets of CRMs to modulate their activities. TRMs transcend TR classification into ubiquitous versus liver-identity factors, as well as TR grouping into functional families. Hence, hierarchical superimpositions of obligatory and facultative TRMs bring about independent transcriptional regulatory inputs defining different sets of CRMs with logical connection to regulation of specific gene sets and biological pathways. Altogether, our study reveals novel principles of concerted transcriptional regulation by multiple TRs at CRMs.}},
  author       = {{Dubois-Chevalier, Julie and Dubois, Vanessa and Dehondt, Helene and Mazrooei, Parisa and Mazuy, Claire and Serandour, Aurelien A. and Gheeraert, Celine and Guillaume, Penderia and Bauge, Eric and Derudas, Bruno and Hennuyer, Nathalie and Paumelle, Rejane and Marot, Guillemette and Carroll, Jason S. and Lupien, Mathieu and Staels, Bart and Lefebvre, Philippe and Eeckhoute, Jerome}},
  issn         = {{1088-9051}},
  journal      = {{GENOME RESEARCH}},
  keywords     = {{ACTIVATED RECEPTOR-GAMMA,TOPOLOGICAL DOMAINS,ENRICHMENT ANALYSIS,GENE-TRANSCRIPTION,LIPID-METABOLISM,EXPRESSION,BINDING,FXR,ENHANCERS,ALPHA}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{985--996}},
  title        = {{The logic of transcriptional regulator recruitment architecture at cis-regulatory modules controlling liver functions}},
  url          = {{http://doi.org/10.1101/gr.217075.116}},
  volume       = {{27}},
  year         = {{2017}},
}
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