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Defining specificity of transcription factor regulatory activities
Jéröme Eeckhoute, Raphaël Métivier, Gilles Salbert


Mammalian transcription factors (TFs) are often involved in differential cell-type- and context-specific transcriptional responses. Recent large-scale comparative studies of TF recruitment to the genome, and of chromatin structure and gene expression, have allowed a better understanding of the general rules that underlie the differential activities of a given TF. It has emerged that chromatin structure dictates the differential binding of a given TF to cell-type-specific cis-regulatory elements. The subsequent regulation of TF activity then ensures the functional activation of only the precise subset of all regulatory sites bound by the TF that are required to mediate appropriate gene expression. Ultimately, the organization of the genome within the nucleus, and crosstalk between different cis-regulatory regions involved in gene regulation, also participate in establishing a specific transcriptional program. In this Commentary, we discuss how the integration of these different and probably intimately linked regulatory mechanisms allow for TF cell-type- and context-specific modulation of gene expression.


  • J.E., R.M. and G.S. are supported by funds from the Centre National de la Recherche Scientifique, Ligue contre le cancer (équipe labellisée 2009), Région Bretagne, Ministère de l'enseignement supérieur et de la recherche and Université de Rennes 1.

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