title: Art27 interacts with GATA4, FOG2 and NKX2.5 and is a novel co-repressor of cardiac genes.
abstract: Transcription factors play a crucial role in regulation of cardiac biology. FOG-2 is indispensable in this setting, predominantly functioning through a physical interaction with GATA-4. This study aimed to identify novel co-regulators of FOG-2 to further elaborate on its inhibitory activity on GATA-4. The Art27 transcription factor was identified by a yeast-2-hybrid library screen to be a novel FOG-2 protein partner. Characterisation revealed that Art27 is co-expressed with FOG-2 and GATA-4 throughout cardiac myocyte differentiation and in multiple structures of the adult heart. Art27 physically interacts with GATA-4, FOG-2 and other cardiac transcription factors and by this means, down-regulates their activity on cardiac specific promoters α-myosin heavy chain, atrial natriuretic peptide and B-type natriuretic peptide. Regulation of endogenous cardiac genes by Art27 was shown using microarray analysis of P19CL6-Mlc2v-GFP cardiomyocytes. Together these results suggest that Art27 is a novel transcription factor that is involved in downregulation of cardiac specific genes by physically interacting and inhibiting the activity of crucial transcriptions factors involved in cardiac biology.
authors.affiliation: Centre for Vascular Research, Department of Medicine, St. George Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Carter
authors.affiliation: Centre for Vascular Research, Department of Medicine, St. George Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Buckle
authors.affiliation: Centre for Vascular Research, Department of Medicine, St. George Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Centre for Vascular Research, Department of Medicine, St. George Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Jose
authors.initials: J
authors.lastname: Perdomo
authors.affiliation: Centre for Vascular Research, Department of Medicine, St. George Clinical School, University of New South Wales, Sydney, New South Wales, Australia; Haematology Department, St George and Sutherland Hospitals, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Beng H
authors.initials: BH
authors.lastname: Chong
mesh_terms: D000328:Adult; D018797:Cell Cycle Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D024723:Ventricular Myosins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D018832:Molecular Chaperones; C095552:NKX2-5 protein, human; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C118920:UXT protein, human; C117427:ZFPM2 protein, human; D024723:Ventricular Myosins
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