Art27 interacts with GATA4, FOG2 and NKX2.5 and is a novel co-repressor of cardiac genes

Daniel R Carter; Andrew D Buckle; Kumiko Tanaka; Jose Perdomo; Beng H Chong

doi:10.1371/journal.pone.0095253

Art27 interacts with GATA4, FOG2 and NKX2.5 and is a novel co-repressor of cardiac genes

PLoS One. 2014 Apr 17;9(4):e95253. doi: 10.1371/journal.pone.0095253. eCollection 2014.

Authors

Daniel R Carter¹, Andrew D Buckle¹, Kumiko Tanaka¹, Jose Perdomo¹, Beng H Chong²

Affiliations

¹ Centre for Vascular Research, Department of Medicine, St. George Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
² 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cell Cycle Proteins
Cell Line
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
GATA4 Transcription Factor / genetics
GATA4 Transcription Factor / metabolism*
Gene Expression Regulation / physiology
Homeobox Protein Nkx-2.5
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism*
Humans
Molecular Chaperones
Myocytes, Cardiac / cytology
Myocytes, Cardiac / metabolism*
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism*
Repressor Proteins / genetics
Repressor Proteins / metabolism*
Transcription Factors / genetics
Transcription Factors / metabolism*
Ventricular Myosins / biosynthesis
Ventricular Myosins / genetics

Substances

Cell Cycle Proteins
DNA-Binding Proteins
GATA4 Transcription Factor
GATA4 protein, human
Homeobox Protein Nkx-2.5
Homeodomain Proteins
Molecular Chaperones
NKX2-5 protein, human
Neoplasm Proteins
Repressor Proteins
Transcription Factors
UXT protein, human
ZFPM2 protein, human
Ventricular Myosins

Grants and funding

This work was supported by a Project Grant from NHMRC, Australia linked to BHC (APP1012409). DRC and ADB were supported by the Australian Postgraduate Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.