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Publication : An integrated holo-enhancer unit defines tissue and gene specificity of the Fgf8 regulatory landscape.

First Author  Marinić M Year  2013
Journal  Dev Cell Volume  24
Issue  5 Pages  530-42
PubMed ID  23453598 Mgi Jnum  J:196292
Mgi Id  MGI:5487697 Doi  10.1016/j.devcel.2013.01.025
Citation  Marinic M, et al. (2013) An integrated holo-enhancer unit defines tissue and gene specificity of the Fgf8 regulatory landscape. Dev Cell 24(5):530-42
abstractText  Fgf8 encodes a key signaling factor, and its precise regulation is essential for embryo patterning. Here, we identified the regulatory modules that control Fgf8 expression during mammalian embryogenesis. These enhancers are interspersed with unrelated genes along a large region of 220 kb; yet they act on Fgf8 only. Intriguingly, this region also contains additional genuine enhancer activities that are not transformed into gene expression. Using genomic engineering strategies, we showed that these multiple and distinct regulatory modules act as a coherent unit and influence genes depending on their position rather than on their promoter sequence. These findings highlight how the structure of a locus regulates the autonomous intrinsic activities of the regulatory elements it contains and contributes to their tissue and target specificities. We discuss the implications of such regulatory systems regarding the evolution of gene expression and the impact of human genomic structural variations.
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