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The HIRA gene lies within the 22q11.2 deletion syndrome critical region; individuals with this syndrome have multiple congenital heart defects. Because terminally differentiated cardiomyocytes have exited the cell cycle, histone variants should be utilized for the bulk of chromatin remodeling. Thus, HIRA is likely to play an important role in epigenetically defining the cardiac gene expression program. In this study, we determined the consequence of HIRA deficiency in cardiomyocytes in vivo by studying the phenotype of cardiomyocyte-specific Hira conditional-knockout mice. Loss of HIRA did not perturb heart development, but instead resulted in cardiomyocyte hypertrophy and susceptibility to sarcolemmal damage. Cardiomyocyte degeneration gave way to focal replacement fibrosis and impaired cardiac function. Gene expression was widely altered in Hira conditional-knockout hearts. Significantly affected pathways included responses to cellular stress, DNA repair and transcription. Consistent with heart failure, fetal cardiac genes were re-expressed in the Hira conditional knockout. Our results suggest that transcriptional regulation by HIRA is crucial for cardiomyocyte homeostasis.<\/jats:p>","DOI":"10.1242\/dmm.022889","type":"journal-article","created":{"date-parts":[[2016,3,2]],"date-time":"2016-03-02T11:30:22Z","timestamp":1456918222000},"page":"335-345","source":"Crossref","is-referenced-by-count":25,"title":["Cardiomyocyte-specific conditional knockout of the histone chaperone HIRA in mice results in hypertrophy, sarcolemmal damage and focal replacement fibrosis"],"prefix":"10.1242","volume":"9","author":[{"given":"Nicolas","family":"Valenzuela","sequence":"first","affiliation":[{"name":"Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiying","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal","family":"Fa'ak","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Soibam","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering Technology, University of Houston-Downtown, Houston, TX 77002, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harika","family":"Nagandla","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA"},{"name":"Stem Cell Engineering Department, Texas Heart Institute at St Luke's Episcopal Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley K.","family":"McConnell","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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