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Series GSE9652 Query DataSets for GSE9652
Status Public on Jul 01, 2008
Title GATA4 is a direct activator of Cyclin D2 and is required for proliferation in 2nd heart field-derived myocardium
Organism Mus musculus
Experiment type Expression profiling by array
Summary The second heart field (SHF) comprises a population of mesodermal progenitor cells that are added to the nascent linear heart to give rise to the majority of the right ventricle, interventricular septum, and outflow tract of mammals and birds. The zinc finger transcription factor GATA4 functions as an integral member of the cardiac transcription factor network in the SHF and its derivatives. In addition to its role in cardiac differentiation, GATA4 is also required for cardiomyocyte replication, although the transcriptional targets of GATA4 required for proliferation have not been previously identified. In the present study, we disrupted Gata4 function exclusively in the SHF and its derivatives. Gata4 SHF knockout mice die by embryonic day 13.5 and exhibit hypoplasia of the right ventricular myocardium and interventricular septum and display profound ventricular septal defects. Loss of Gata4 function in the SHF results in decreased myocyte proliferation in the right ventricle, and we identify numerous cell cycle genes that are dependent on Gata4 by microarray analysis. We show that Gata4 is required for Cyclin D2 expression in the right ventricle and that the Cyclin D2 promoter is bound and activated by GATA4 via three consensus GATA binding sites. These findings establish Cyclin D2 as a direct transcriptional target of GATA4 and support a model in which GATA4 controls cardiomyocyte proliferation by coordinately regulating numerous cell cycle genes.
Keywords: genetic modification
 
Overall design Onewat ANOVA with post-hoc was done with 3 genotypes with replicates. Three genetypes are Gata4flox/+; Nkx2-5+/+ (control, n=3), Gata4flox/+; Nkx2-5Cre/+ (Gata4; Nkx2-5 double heterozygous,
170 n=3), and Gata4flox/flox; Nkx2-5Cre/+ (Gata4 CKONkx, n=5).
 
Contributor(s) Rojas A, Kong S, Pu WT, Black BL
Citation(s) 18591257
Submission date Nov 21, 2007
Last update date Feb 11, 2019
Contact name Sek Won Kong
E-mail(s) swkong@enders.tch.harvard.edu
Phone 617-919-2689
Organization name Boston Children's Hospital
Department Informatics Program
Lab EN137
Street address 300 Longwood Avenue
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (11)
GSM243911 Gata4 flox/+ ; Nkx2-5 +/+ rep1
GSM243912 Gata4 flox/+ ; Nkx2-5 +/+ rep2
GSM243913 Gata4 flox/+ ; Nkx2-5 +/+ rep3
Relations
BioProject PRJNA103521

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE9652_RAW.tar 38.3 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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