title: skNAC and Smyd1 in transcriptional control.
abstract: Skeletal and heart muscle-specific variant of the alpha subunit of nascent polypeptide associated complex (skNAC) is exclusively found in striated muscle cells. Its function, however, is largely unknown. Previous reports could demonstrate that skNAC binds to Smyd1 (SET and MYND domain containing protein 1). The facts that (a) SET domains have histone methyltransferase activity, and (b) MYND domains are known recruiters of histone deacetylases (HDACs), implicate the skNAC-Smyd1 complex in transcriptional control. To study potential target genes, we carried out cDNA microarray analysis on differentiating C2C12 myoblasts in which expression of the skNAC gene had been knocked down. We found and confirmed a series of targets, specifically genes encoding regulators of inflammation, cellular metabolism, and cell migration. Mechanistically, as shown by Western blot, ELISA, and ChIP analysis at selected promoter regions, transcriptional control by skNAC-Smyd1 appears to be exerted at least in part by affecting a series of histone modifications, specifically H3K4 di- and trimethylation and potentially also histone acetylation. Taken together, our data suggest that the skNAC-Smyd1 complex is involved in transcriptional regulation both via the control of histone methylation and histone (de)acetylation.
authors.affiliation: Charité-University Medicine Berlin, Institute of Physiology, Charitéplatz 1, D-10117 Berlin, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Berkholz
authors.affiliation: Free University of Berlin, Department of Biology, Chemistry, and Pharmacy, Institute of Chemistry and Biochemistry, Ihnestr. 73, D-14195 Berlin, Germany; Max Planck Institute for Molecular Genetics, Development and Disease, Ihnestr. 73, D-14195 Berlin, Germany.
authors.forename: Mickael
authors.initials: M
authors.lastname: Orgeur
authors.affiliation: Free University of Berlin, Department of Biology, Chemistry, and Pharmacy, Institute of Chemistry and Biochemistry, Ihnestr. 73, D-14195 Berlin, Germany; Max Planck Institute for Molecular Genetics, Development and Disease, Ihnestr. 73, D-14195 Berlin, Germany.
authors.forename: Sigmar
authors.initials: S
authors.lastname: Stricker
authors.affiliation: University Hospital Tubingen, Medical Clinic, Department of Sports Medicine, Hoppe-Seyler-Str. 6, D-72076 Tubingen, Germany. Electronic address: barbara.munz@med.uni-tuebingen.de.
authors.forename: Barbara
authors.initials: B
authors.lastname: Munz
mesh_terms: D000107:Acetylation; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D007249:Inflammation / Q000235:genetics; D008745:Methylation; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics*; D009124:Muscle Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism; D032386:Myoblasts, Cardiac / Q000166:cytology; D032448:Myoblasts, Skeletal / Q000166:cytology; D009206:Myocardium / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*; D020663:ras Guanine Nucleotide Exchange Factors / Q000096:biosynthesis
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; D018832:Molecular Chaperones; D009124:Muscle Proteins; D034741:RNA, Small Interfering; C504491:Rasgrf2 protein, mouse; C096485:Smyd1 protein, mouse; D014157:Transcription Factors; C096099:nascent-polypeptide-associated complex; D020663:ras Guanine Nucleotide Exchange Factors; D013385:Succinate Dehydrogenase; D006655:Histone Deacetylases
keywords: HDACs; HMTs; Myogenic differentiation; Smyd1/m-Bop; skNAC