Secondary enhancers synergise with primary enhancers to guarantee fine-tuned muscle gene expression

Guerrero, LuciaMarco Ferreres, RaquelSerrano, Antonio L.Arredondo, Juan JoseCervera, Margarita2015-06-042015-06-042010Guerrero L, Marco-Ferreres R, Serrano AL, Arredondo JJ, Cervera M. Secondary enhancers synergise with primary enhancers to guarantee fine-tuned muscle gene expression. Developmental Biology. 2010;337(1):16-28. DOI: 10.1016/j.ydbio.2009.10.0060012-1606http://hdl.handle.net/10230/23728Although tight quantitative control of gene expression is required to ensure that organs and tissues function correctly, the transcriptional mechanisms underlying this process still remain poorly understood. Here, we describe novel and evolutionary conserved secondary enhancers that are needed for the regulation of the expression of Troponin I genes. Secondary enhancers are silent when tested individually in electroporated muscles but interact with the primary enhancers and are required to precisely control the appropriate timing, the tissue and fibre specificity, and the quantitative expression of these genes during muscle differentiation. Synergism is completely dependent of the fully conserved MEF2 site present on the primary enhancers core of skeletal muscle Troponin I genes. Thus, while each of these paired enhancers has a different function, the concerted action of both is crucial to recapitulate endogenous gene expression. Through comparative genomics, we predict that this mechanism has also arisen in other mammalian muscle genes. Our results reveal the existence of a novel mechanism, conserved from flies to mammals, to fine-tune gene expression in each muscle and probably other tissuesapplication/pdfeng© Elsevier This is the published version of an article http://dx.doi.org/10.1016/j.ydbio.2009.10.006 that appeared in the journal Developmental Biology. It is published in an Open Archive under an Elsevier user license. Details of this licence are available here: http://www.elsevier.com/about/open-access/open-access-policies/oa-license-policy/elsevier-user-licenseRatolins (Animals de laboratori)Genètica animalSecondary enhancers synergise with primary enhancers to guarantee fine-tuned muscle gene expressioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.ydbio.2009.10.006Paired enhancersSecondary enhancersFine-tuning gene-transcription controlGlobal transcription regulationMouse fast, slow and cardiac Troponin I genesinfo:eu-repo/semantics/openAccess