{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:02:24Z","timestamp":1791576144263,"version":"4.3.4"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2014,3,28]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Histone deacetylases (HDACs) are closely involved in cardiac reprogramming. Although the functional roles of class I and class IIa HDACs are well established, the significance of interclass crosstalk in the development of cardiac hypertrophy remains unclear.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Recently, we suggested that casein kinase 2\u03b11\u2013dependent phosphorylation of HDAC2 leads to enzymatic activation, which in turn induces cardiac hypertrophy. Here we report an alternative post-translational activation mechanism of HDAC2 that involves acetylation of HDAC2 mediated by p300\/CBP-associated factor\/HDAC5.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Hdac2 was acetylated in response to hypertrophic stresses in both cardiomyocytes and a mouse model. Acetylation was reduced by a histone acetyltransferase inhibitor but was increased by a nonspecific HDAC inhibitor. The enzymatic activity of Hdac2 was positively correlated with its acetylation status. p300\/CBP-associated factor bound to Hdac2 and induced acetylation. The HDAC2 K75 residue was responsible for hypertrophic stress\u2013induced acetylation. The acetylation-resistant Hdac2 K75R showed a significant decrease in phosphorylation on S394, which led to the loss of intrinsic activity. Hdac5, one of class IIa HDACs, directly deacetylated Hdac2. Acetylation of Hdac2 was increased in Hdac5-null mice. When an acetylation-mimicking mutant of Hdac2 was infected into cardiomyocytes, the antihypertrophic effect of either nuclear tethering of Hdac5 with leptomycin B or Hdac5 overexpression was reduced.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Taken together, our results suggest a novel mechanism by which the balance of HDAC2 acetylation is regulated by p300\/CBP-associated factor and HDAC5 in the development of cardiac hypertrophy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.114.303429","type":"journal-article","created":{"date-parts":[[2014,2,14]],"date-time":"2014-02-14T02:11:09Z","timestamp":1392343869000},"page":"1133-1143","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":74,"title":["Regulation of Acetylation of Histone Deacetylase 2 by p300\/CBP-Associated Factor\/Histone Deacetylase 5 in the Development of Cardiac Hypertrophy"],"prefix":"10.1161","volume":"114","author":[{"given":"Gwang Hyeon","family":"Eom","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology (G.H.E., J.-K.K., H.K.) and Medical Research Center for Gene Regulation (G.H.E., Y.S.N., N.C., H.-K.M., H.K.), Chonnam National University Medical School, Gwangju, Republic of Korea; Global Research Laboratory and College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea (J.G.O., W.J.P.); Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea (E.-K.Y., I.-K.L.); Division..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon Seok","family":"Nam","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (G.H.E., J.-K.K., H.K.) and Medical Research Center for Gene Regulation (G.H.E., Y.S.N., N.C., H.-K.M., H.K.), Chonnam National University Medical School, Gwangju, Republic of Korea; Global Research Laboratory and College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea (J.G.O., W.J.P.); Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea (E.-K.Y., I.-K.L.); Division..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Gyun","family":"Oh","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (G.H.E., J.-K.K., H.K.) and Medical Research Center for Gene Regulation (G.H.E., Y.S.N., N.C., H.-K.M., H.K.), Chonnam National University Medical School, Gwangju, Republic of Korea; Global Research Laboratory and College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea (J.G.O., W.J.P.); Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea (E.-K.Y., I.-K.L.); Division..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nakwon","family":"Choe","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (G.H.E., J.-K.K., H.K.) and Medical Research Center for Gene Regulation (G.H.E., Y.S.N., N.C., H.-K.M., H.K.), Chonnam National University Medical School, Gwangju, Republic of Korea; Global Research Laboratory and College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea (J.G.O., W.J.P.); Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea (E.-K.Y., I.-K.L.); Division..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Ki","family":"Min","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (G.H.E., J.-K.K., H.K.) and Medical Research Center for Gene Regulation (G.H.E., Y.S.N., N.C., H.-K.M., H.K.), Chonnam National University Medical School, Gwangju, Republic of Korea; Global Research Laboratory and College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea (J.G.O., W.J.P.); Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea (E.-K.Y., I.-K.L.); Division..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Kyung","family":"Yoo","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (G.H.E., J.-K.K., H.K.) and Medical Research Center for Gene Regulation (G.H.E., Y.S.N., N.C., H.-K.M., H.K.), Chonnam National University Medical School, Gwangju, Republic of Korea; Global Research Laboratory and College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea (J.G.O., W.J.P.); Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea (E.-K.Y., I.-K.L.); 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Division..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Keun","family":"Kim","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (G.H.E., J.-K.K., H.K.) and Medical Research Center for Gene Regulation (G.H.E., Y.S.N., N.C., H.-K.M., H.K.), Chonnam National University Medical School, Gwangju, Republic of Korea; Global Research Laboratory and College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea (J.G.O., W.J.P.); Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea (E.-K.Y., I.-K.L.); Division..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In-Kyu","family":"Lee","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (G.H.E., J.-K.K., H.K.) and Medical Research Center for Gene Regulation (G.H.E., Y.S.N., N.C., H.-K.M., H.K.), Chonnam National University Medical School, Gwangju, Republic of Korea; Global Research Laboratory and College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea (J.G.O., W.J.P.); Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea (E.-K.Y., I.-K.L.); Division..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhonda","family":"Bassel-Duby","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (G.H.E., J.-K.K., H.K.) and Medical Research Center for Gene Regulation (G.H.E., Y.S.N., N.C., H.-K.M., H.K.), Chonnam National University Medical School, Gwangju, Republic of Korea; Global Research Laboratory and College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea (J.G.O., W.J.P.); Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea (E.-K.Y., I.-K.L.); 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