Xuan Chi, Pradeep K Chatterjee, Willie Wilson, Shu-Xing Zhang, Franco J Demayo, Robert J Schwartz
Graduate Program in Cardiovascular Sciences and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Proceedings of the National Academy of Sciences of the United States of America 2005 Sep 20We previously reported that an Nkx2-5-GFP bacterial artificial chromosome in transgenic mice recapitulated the endogenous gene activity in the heart. Here, we identified three additional previously uncharacterized distal enhancer modules of Nkx2-5: UH6, which directed transgene expression in the right ventricle, interventricular septum, and atrial ventricular canal; UH5, which directed expression in both atria; and UH4, which directed transgene expression in tongue muscle. Nkx2-5 enhancers drive cardiogenic gene activity from the earliest progenitors to the late-stage embryonic heart, reside within its 27 kb of 5' flanking sequences, organized in a tandem array. Nkx2-5 enhancers involved with stomach-, tongue-, and chamber-restricted expression displayed lacZ transgene activity and chromatin histone acetylation patterns consistent with tissue-specific expression. An examination of Nkx2-5 gene activity in murine embryonic stem cells converted to beating embryoid bodies showed that only the proximal active region 2 and GATA-Smad enhancers were chromatin-remodeled. Chromatin remodeling of active region 2 and GATA-Smad enhancers were blunted by noggin coexpression, which indicated dependence on bone morphogenetic protein signaling for their chromatin activation during activation of Nkx2-5 expression.
Xuan Chi, Pradeep K Chatterjee, Willie Wilson, Shu-Xing Zhang, Franco J Demayo, Robert J Schwartz. Complex cardiac Nkx2-5 gene expression activated by noggin-sensitive enhancers followed by chamber-specific modules. Proceedings of the National Academy of Sciences of the United States of America. 2005 Sep 20;102(38):13490-5
PMID: 16150722
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