Open AccessThe SRCAP chromatin remodeling complex promotes oxidative metabolism during prenatal heart development
Author(s) -
Mingjie Xu,
Jie Yao,
Yingchao Shi,
Huijuan Yi,
Wukui Zhao,
Xinhua Lin,
Zhongzhou Yang
Publication year - 2021
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.199026
Subject(s) - biology , oxidative phosphorylation , microbiology and biotechnology , mitochondrion , chromatin remodeling , transcription factor , anaerobic glycolysis , glycolysis , transcriptional regulation , citric acid cycle , transcription (linguistics) , metabolism , biochemistry , gene , linguistics , philosophy
Mammalian heart development relies on cardiomyocyte mitochondrial maturation and metabolism. Embryonic cardiomyocytes make a metabolic shift from anaerobic glycolysis to oxidative metabolism by mid-gestation. VHL-HIF signaling favors anaerobic glycolysis but this process subsides by E14.5. Meanwhile, oxidative metabolism becomes activated but its regulation is largely elusive. Here, we first pinpointed a crucial temporal window for mitochondrial maturation and metabolic shift, and uncovered the pivotal role of the SRCAP chromatin remodeling complex in these processes in mouse. Disruption of this complex massively suppressed the transcription of key genes required for the tricarboxylic acid cycle, fatty acid β-oxidation and ubiquinone biosynthesis, and destroyed respirasome stability. Furthermore, we found that the SRCAP complex functioned through H2A.Z deposition to activate transcription of metabolic genes. These findings have unveiled the important physiological functions of the SRCAP complex in regulating mitochondrial maturation and promoting oxidative metabolism during heart development, and shed new light on the transcriptional regulation of ubiquinone biosynthesis.