{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:11:06Z","timestamp":1781104266552,"version":"3.54.1"},"reference-count":49,"publisher":"National Academy of Sciences","issue":"38","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,9,20]]},"abstract":"<jats:p>\n                    We 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\u2032 flanking sequences, organized in a tandem array. Nkx2-5 enhancers involved with stomach-, tongue-, and chamber-restricted expression displayed\n                    <jats:italic>lacZ<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0504295102","type":"journal-article","created":{"date-parts":[[2005,9,6]],"date-time":"2005-09-06T20:33:41Z","timestamp":1126038821000},"page":"13490-13495","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":31,"title":["Complex cardiac Nkx2-5 gene expression activated by noggin-sensitive enhancers followed by chamber-specific modules"],"prefix":"10.1073","volume":"102","author":[{"given":"Xuan","family":"Chi","sequence":"first","affiliation":[{"name":"Graduate Program in Cardiovascular Sciences and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030; Julius L. Chambers Biomedical\/Biotechnology Research Institute and Department of Biology, North Carolina Central University, Durham, NC 27707; and Center for Molecular Development and Disease, Institute of Biosciences and Technology, Texas A&amp;M University Health Science Center, 2121 West Holcombe, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep K.","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Graduate Program in Cardiovascular Sciences and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030; Julius L. 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