title: Sertad1 encodes a novel transcriptional co-activator of SMAD1 in mouse embryonic hearts.
abstract: Despite considerable advances in surgical repairing procedures, congenital heart diseases (CHDs) remain the leading noninfectious cause of infant morbidity and mortality. Understanding the molecular/genetic mechanisms underlying normal cardiogenesis will provide essential information for the development of novel diagnostic and therapeutic strategies against CHDs. BMP signaling plays complex roles in multiple cardiogenic processes in mammals. SMAD1 is a canonical nuclear mediator of BMP signaling, the activity of which is critically regulated through its interaction partners. We screened a mouse embryonic heart yeast two-hybrid library using Smad1 as bait and identified SERTAD1 as a novel interaction partner of SMAD1. SERTAD1 contains multiple potential functional domains, including two partially overlapping transactivation domains at the C terminus. The SERTAD1-SMAD1 interaction in vitro and in mammalian cells was further confirmed through biochemical assays. The expression of Sertad1 in developing hearts was demonstrated using RT-PCR, western blotting and in situ hybridization analyses. We also showed that SERTAD1 was localized in both the cytoplasm and nucleus of immortalized cardiomyocytes and primary embryonic cardiomyocyte cultures. The overexpression of SERTAD1 in cardiomyocytes not only enhanced the activity of two BMP reporters in a dose-dependent manner but also increased the expression of several known BMP/SMAD regulatory targets. Therefore, these data suggest that SERTAD1 acts as a SMAD1 transcriptional co-activator to promote the expression of BMP target genes during mouse cardiogenesis.
authors.affiliation: Department of Genetics, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Yin
authors.initials: Y
authors.lastname: Peng
authors.forename: Shaomin
authors.initials: S
authors.lastname: Zhao
authors.forename: Langying
authors.initials: L
authors.lastname: Song
authors.forename: Manyuan
authors.initials: M
authors.lastname: Wang
authors.forename: Kai
authors.initials: K
authors.lastname: Jiao
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D038081:Organogenesis / Q000235:genetics; D051898:Smad1 Protein / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D000092468:Bromodomain Containing Proteins
chemical_list: D019485:Bone Morphogenetic Proteins; D009687:Nuclear Proteins; D051898:Smad1 Protein; D015534:Trans-Activators; D014157:Transcription Factors; C485730:Sertad1 protein, mouse; D000092468:Bromodomain Containing Proteins; C497401:Smad1 protein, mouse
keywords: BMP signaling; Cardiogenesis; SMAD1; Transcriptional co-activator; Yeast two-hybrid