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Impact of ATP1B4 Gene Co‐option on Perinatal Development of Placental Mammals
Author(s) -
Modyanov Nikolai,
Serna Ivana,
Ahmad Nisar,
Russo Lucia,
Pestov Nikolay,
Najjar Sonia
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.684.1
Subject(s) - myod , biology , skeletal muscle , gene , endocrinology , medicine , regulation of gene expression , microbiology and biotechnology , myocyte , myogenesis , genetics
Vertebrate X‐chromosome ATP1B4 genes represent a rare instance of orthologous gene co‐option that transformed Na,K‐ATPase BetaM subunit of lower vertebrates into eutherian skeletal and cardiac muscle‐specific BetaM protein of the inner nuclear membrane. BetaM is expressed at the highest level during late fetal and early postnatal development and is implicated in the regulation of gene expression. We show that BetaM is a component of MyoD, MyoG and Smad7 transcriptional complexes in neonatal skeletal muscle and up‐regulates MyoD expression in cultured muscle cells by altering chromatin structure and recruiting SWI/SNF to the MyoD promoter. Notably, Atp1b4 ablation in mice results in significantly lower body weight, growth retardation and high mortality of knockout neonates. Moreover,mRNA sequencing of skeletal muscle from neonatal WT and KO male littermates revealed broad changes in expression of genes important for lipid metabolism and thermoregulation as well as down regulation of fast‐twitch and up‐regulation of slow‐twitch muscle genes. These data indicate that BetaM plays an important role during a critical period of perinatal and neonatal development of placental mammals and that evolutionarily acquired new functions of BetaM proteins are physiologically essential, even might be necessary for survival of placental mammals in natural conditions, and provide an evolutionary advantage. Supported by Dept. of Physiology & Pharmacology and Center for Diabetes and Endocrine Research, UT COM