NKX2-5 regulates the expression of beta-catenin and GATA4 in ventricular myocytes

Autor: Glen S. Van Arsdell, Syed H.E. Zaidi, Jun K. Takeuchi, Fariba Amini, Benoit G. Bruneau, Lisa K. Hornberger, John G. Coles, Ali M. Riazi
Přispěvatelé: Fugmann, Sebastian D
Rok vydání: 2009
Předmět:
Messenger
lcsh:Medicine
Electrophoretic Mobility Shift Assay
Cardiovascular
Mice
0302 clinical medicine
Models
Gene expression
2.1 Biological and endogenous factors
Myocytes
Cardiac
Aetiology
lcsh:Science
Promoter Regions
Genetic
beta Catenin
Regulation of gene expression
0303 health sciences
Multidisciplinary
biology
Genetics and Genomics/Gene Expression
respiratory system
Heart Disease
030220 oncology & carcinogenesis
embryonic structures
cardiovascular system
Homeobox Protein Nkx-2.5
Biochemistry/Transcription and Translation
Cardiac
Research Article
Protein Binding
endocrine system
Chromatin Immunoprecipitation
Heterozygote
Beta-catenin
General Science & Technology
Heart Ventricles
Molecular Sequence Data
Promoter Regions
03 medical and health sciences
Downregulation and upregulation
stomatognathic system
Genetic
Genetics
Animals
Humans
RNA
Messenger
Transcription factor
030304 developmental biology
Homeodomain Proteins
Reporter gene
Myocytes
Binding Sites
Models
Genetic
Base Sequence
lcsh:R
Promoter
Molecular biology
GATA4 Transcription Factor
Wnt Proteins
Gene Expression Regulation
Developmental Biology/Cell Differentiation
biology.protein
RNA
lcsh:Q
Chromatin immunoprecipitation
Transcription Factors
Zdroj: PloS one, vol 4, iss 5
PLoS ONE
PLoS ONE, Vol 4, Iss 5, p e5698 (2009)
Popis: Author(s): Riazi, Ali M; Takeuchi, Jun K; Hornberger, Lisa K; Zaidi, Syed Hassan; Amini, Fariba; Coles, John; Bruneau, Benoit G; Van Arsdell, Glen S | Abstract: BackgroundThe molecular pathway that controls cardiogenesis is temporally and spatially regulated by master transcriptional regulators such as NKX2-5, Isl1, MEF2C, GATA4, and beta-catenin. The interplay between these factors and their downstream targets are not completely understood. Here, we studied regulation of beta-catenin and GATA4 by NKX2-5 in human fetal cardiac myocytes.Methodology/principal findingsUsing antisense inhibition we disrupted the expression of NKX2-5 and studied changes in expression of cardiac-associated genes. Down-regulation of NKX2-5 resulted in increased beta-catenin while GATA4 was decreased. We demonstrated that this regulation was conferred by binding of NKX2-5 to specific elements (NKEs) in the promoter region of the beta-catenin and GATA4 genes. Using promoter-luciferase reporter assay combined with mutational analysis of the NKEs we demonstrated that the identified NKX2-5 binding sites were essential for the suppression of beta-catenin, and upregulation of GATA4 by NKX2-5.ConclusionsThis study suggests that NKX2-5 modulates the beta-catenin and GATA4 transcriptional activities in developing human cardiac myocytes.
Databáze: OpenAIRE
Externí odkaz: