{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T23:05:43Z","timestamp":1773270343043,"version":"3.50.1"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2010,4,2]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Rationale<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            The transcriptional networks guiding heart development remain poorly understood, despite the identification of several essential cardiac transcription factors.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Objective<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            To isolate novel cardiac transcription factors, we performed gene chip analysis and found that\n            <jats:italic>Zac1<\/jats:italic>\n            , a zinc finger-type transcription factor, was strongly expressed in the developing heart. This study was designed to investigate the molecular and functional role of Zac1 as a cardiac transcription factor.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Methods and Results<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            Zac1 was strongly expressed in the heart from cardiac crescent stages and in the looping heart showed a chamber-restricted pattern. Zac1 stimulated luciferase reporter constructs driven by\n            <jats:italic>ANF, BNP<\/jats:italic>\n            , or \u03b1\n            <jats:italic>MHC<\/jats:italic>\n            promoters. Strong functional synergy was seen between Zac1 and Nkx2-5 on the\n            <jats:italic>ANF<\/jats:italic>\n            promoter, which carries adjacent Zac1 and Nkx2-5 DNA-binding sites. Zac1 directly associated with the\n            <jats:italic>ANF<\/jats:italic>\n            promoter in vitro and in vivo, and Zac1 and Nkx2-5 physically associated through zinc fingers 5 and 6 in Zac1, and the homeodomain in Nkx2-5.\n            <jats:italic>Zac1<\/jats:italic>\n            is a maternally imprinted gene and is the first such gene found to be involved in heart development. Homozygous and paternally derived heterozygous mice carrying an interruption in the\n            <jats:italic>Zac1<\/jats:italic>\n            locus showed decreased levels of chamber and myofilament genes, increased apoptotic cells, partially penetrant lethality and morphological defects including atrial and ventricular septal defects, and thin ventricular walls.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Conclusions<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            Zac1 plays an essential role in the cardiac gene regulatory network. Our data provide a potential mechanistic link between Zac1 in cardiogenesis and congenital heart disease manifestations associated with genetic or epigenetic defects in an imprinted gene network.\n          <\/jats:p>","DOI":"10.1161\/circresaha.109.214130","type":"journal-article","created":{"date-parts":[[2010,2,19]],"date-time":"2010-02-19T03:24:18Z","timestamp":1266549858000},"page":"1083-1091","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":46,"title":["Zac1 Is an Essential Transcription Factor for Cardiac Morphogenesis"],"prefix":"10.1161","volume":"106","author":[{"given":"Shinsuke","family":"Yuasa","sequence":"first","affiliation":[{"name":"From the Department of Regenerative Medicine and Advanced Cardiac Therapeutics (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., R.K., M.M., F.H., S.M., M.S., K.F.); Cardiology Division (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., M.M., S.O.), Department of Internal Medicine; and Center for Integrated Medical Research (S.Y., S.M.), Keio University School of Medicine, Tokyo, Japan; Victor Chang Cardiac Research Institute (O.W.J.P., R.P.H.), Darlinghurst, New South Wales..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Onizuka","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Advanced Cardiac Therapeutics (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., R.K., M.M., F.H., S.M., M.S., K.F.); Cardiology Division (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., M.M., S.O.), Department of Internal Medicine; and Center for Integrated Medical Research (S.Y., S.M.), Keio University School of Medicine, Tokyo, Japan; Victor Chang Cardiac Research Institute (O.W.J.P., R.P.H.), Darlinghurst, New South Wales..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenichiro","family":"Shimoji","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Advanced Cardiac Therapeutics (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., R.K., M.M., F.H., S.M., M.S., K.F.); Cardiology Division (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., M.M., S.O.), Department of Internal Medicine; and Center for Integrated Medical Research (S.Y., S.M.), Keio University School of Medicine, Tokyo, Japan; Victor Chang Cardiac Research Institute (O.W.J.P., R.P.H.), Darlinghurst, New South Wales..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohei","family":"Ohno","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Advanced Cardiac Therapeutics (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., R.K., M.M., F.H., S.M., M.S., K.F.); Cardiology Division (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., M.M., S.O.), Department of Internal Medicine; and Center for Integrated Medical Research (S.Y., S.M.), Keio University School of Medicine, Tokyo, Japan; Victor Chang Cardiac Research Institute (O.W.J.P., R.P.H.), Darlinghurst, New South Wales..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshimi","family":"Kageyama","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Advanced Cardiac Therapeutics (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., R.K., M.M., F.H., S.M., M.S., K.F.); Cardiology Division (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., M.M., S.O.), Department of Internal Medicine; and Center for Integrated Medical Research (S.Y., S.M.), Keio University School of Medicine, Tokyo, Japan; Victor Chang Cardiac Research Institute (O.W.J.P., R.P.H.), Darlinghurst, New South Wales..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Han","family":"Yoon","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Advanced Cardiac Therapeutics (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., R.K., M.M., F.H., S.M., M.S., K.F.); Cardiology Division (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., M.M., S.O.), Department of Internal Medicine; and Center for Integrated Medical Research (S.Y., S.M.), Keio University School of Medicine, Tokyo, Japan; Victor Chang Cardiac Research Institute (O.W.J.P., R.P.H.), Darlinghurst, New South Wales..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toru","family":"Egashira","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Advanced Cardiac Therapeutics (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., R.K., M.M., F.H., S.M., M.S., K.F.); Cardiology Division (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., M.M., S.O.), Department of Internal Medicine; and Center for Integrated Medical Research (S.Y., S.M.), Keio University School of Medicine, Tokyo, Japan; Victor Chang Cardiac Research Institute (O.W.J.P., R.P.H.), Darlinghurst, New South Wales..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohisa","family":"Seki","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Advanced Cardiac Therapeutics (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., R.K., M.M., F.H., S.M., M.S., K.F.); Cardiology Division (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., M.M., S.O.), Department of Internal Medicine; and Center for Integrated Medical Research (S.Y., S.M.), Keio University School of Medicine, Tokyo, Japan; Victor Chang Cardiac Research Institute (O.W.J.P., R.P.H.), Darlinghurst, New South Wales..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisayuki","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Advanced Cardiac Therapeutics (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., R.K., M.M., F.H., S.M., M.S., K.F.); Cardiology Division (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., M.M., S.O.), Department of Internal Medicine; and Center for Integrated Medical Research (S.Y., S.M.), Keio University School of Medicine, Tokyo, Japan; Victor Chang Cardiac Research Institute (O.W.J.P., R.P.H.), Darlinghurst, New South Wales..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiko","family":"Nishiyama","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Advanced Cardiac Therapeutics (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., R.K., M.M., F.H., S.M., M.S., K.F.); Cardiology Division (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., M.M., S.O.), Department of Internal Medicine; and Center for Integrated Medical Research (S.Y., S.M.), Keio University School of Medicine, Tokyo, Japan; Victor Chang Cardiac Research Institute (O.W.J.P., R.P.H.), Darlinghurst, New South Wales..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruri","family":"Kaneda","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Advanced Cardiac Therapeutics (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., R.K., M.M., F.H., S.M., M.S., K.F.); Cardiology Division (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., M.M., S.O.), Department of Internal Medicine; and Center for Integrated Medical Research (S.Y., S.M.), Keio University School of Medicine, Tokyo, Japan; Victor Chang Cardiac Research Institute (O.W.J.P., R.P.H.), Darlinghurst, New South Wales..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsushige","family":"Murata","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Advanced Cardiac Therapeutics (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., R.K., M.M., F.H., S.M., M.S., K.F.); Cardiology Division (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., M.M., S.O.), Department of Internal Medicine; and Center for Integrated Medical Research (S.Y., S.M.), Keio University School of Medicine, Tokyo, Japan; Victor Chang Cardiac Research Institute (O.W.J.P., R.P.H.), Darlinghurst, New South Wales..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumiyuki","family":"Hattori","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Advanced Cardiac Therapeutics (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., R.K., M.M., F.H., S.M., M.S., K.F.); Cardiology Division (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., M.M., S.O.), Department of Internal Medicine; and Center for Integrated Medical Research (S.Y., S.M.), Keio University School of Medicine, Tokyo, Japan; Victor Chang Cardiac Research Institute (O.W.J.P., R.P.H.), Darlinghurst, New South Wales..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Makino","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Advanced Cardiac Therapeutics (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., R.K., M.M., F.H., S.M., M.S., K.F.); Cardiology Division (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., M.M., S.O.), Department of Internal Medicine; and Center for Integrated Medical Research (S.Y., S.M.), Keio University School of Medicine, Tokyo, Japan; Victor Chang Cardiac Research Institute (O.W.J.P., R.P.H.), Darlinghurst, New South Wales..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motoaki","family":"Sano","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Advanced Cardiac Therapeutics (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., R.K., M.M., F.H., S.M., M.S., K.F.); Cardiology Division (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., M.M., S.O.), Department of Internal Medicine; and Center for Integrated Medical Research (S.Y., S.M.), Keio University School of Medicine, Tokyo, Japan; Victor Chang Cardiac Research Institute (O.W.J.P., R.P.H.), Darlinghurst, New South Wales..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Ogawa","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Advanced Cardiac Therapeutics (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., R.K., M.M., F.H., S.M., M.S., K.F.); Cardiology Division (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., M.M., S.O.), Department of Internal Medicine; and Center for Integrated Medical Research (S.Y., S.M.), Keio University School of Medicine, Tokyo, Japan; Victor Chang Cardiac Research Institute (O.W.J.P., R.P.H.), Darlinghurst, New South Wales..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Owen W.J.","family":"Prall","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Advanced Cardiac Therapeutics (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., R.K., M.M., F.H., S.M., M.S., K.F.); Cardiology Division (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., M.M., S.O.), Department of Internal Medicine; and Center for Integrated Medical Research (S.Y., S.M.), Keio University School of Medicine, Tokyo, Japan; Victor Chang Cardiac Research Institute (O.W.J.P., R.P.H.), Darlinghurst, New South Wales..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard P.","family":"Harvey","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Advanced Cardiac Therapeutics (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., R.K., M.M., F.H., S.M., M.S., K.F.); Cardiology Division (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., M.M., S.O.), Department of Internal Medicine; and Center for Integrated Medical Research (S.Y., S.M.), Keio University School of Medicine, Tokyo, Japan; Victor Chang Cardiac Research Institute (O.W.J.P., R.P.H.), Darlinghurst, New South Wales..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiichi","family":"Fukuda","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine and Advanced Cardiac Therapeutics (S.Y., T.O., K.S., Y.O., T.K., S.H.Y., T.E., T.S., H.H., T.N., R.K., M.M., F.H., S.M., M.S., K.F.); 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