Comment[ArrayExpressAccession]	E-MTAB-1821
MAGE-TAB Version	1.1
Investigation Title	Gene profiling of Hand2 target genes and transcriptional regulation of Hand2 expression in the postnatal myocardium
Comment[Submitted Name]	Gene profiling of Hand2 target genes and transcriptional regulation of Hand2 expression in the postnatal myocardium
Experiment Description	In humans, cardiac hypertrophy is the principal risk factor for the development of overt heart failure and sudden cardiac death from lethal arrhythmias. Although aberrant reactivation of  fetal² gene programs is intricately linked to maladaptive hypertrophy of postnatal cardiomyocytes, loss of cardiac function and heart failure, the transcription factors driving these gene programs remain ill defined. We report that the basic helix-loop-helix (bHLH) transcription factor dHAND/Hand2 is re-expressed in the mammalian postnatal myocardium in response to stress signaling. Interestingly, mutant mice overexpressing Hand2 in otherwise healthy ventricular myocytes developed a phenotype of pathological hypertrophy. In contrast, conditional gene-targeted Hand2 mice demonstrated a marked resistance to pressure overload-induced hypertrophy, fibrosis, ventricular dysfunction and induction of a fetal gene program. These data suggest a critical role for the Hand2 transcription factor during hypertrophic remodeling and heart failure. To gain more mechanistically insight in the processes underlying heart failure, we here identified Hand2 target genes by microarray gene expression profiling. RNA samples were collected 4 weeks after sham or TAC surgery (to induce pressure overload) of both tamoxifen-treated Hand2f/f (WT) and MCM-Hand2f/f (KO) mice.
Experimental Design	disease_state_design	in_vivo_design	co-expression_design
Comment[AEExperimentType]	transcription profiling by array
Comment[AEExperimentDisplayName]	Transcription profiling by array of mouse postnatal myocardium collected 4 weeks after sham or TAC surgery from both tamoxifen-treated Hand2f/f (wild type) and MCM-Hand2f/f (knock out) mice to identify Hand2 target genes
Experimental Factor Name	strain	clinical treatment	disease
Experimental Factor Type	strain	clinical treatment	disease
Quality Control Type	biological replicate
Quality Control Term Source REF	EFO
Public Release Date	2013-11-15
Person Last Name	de Windt
Person First Name	Leon
Person Mid Initials	J.
Person Email	l.dewindt@maastrichtuniversity.nl
Person Phone	31634354189
Person Address	Dept. of Cardiology, Universiteitssingel 50, 6229 ER Maastricht, the Netherlands
Person Affiliation	LDW
Person Roles	submitter
PubMed ID	24161931
Publication Author List	Dirkx E, Gladka MM, Philippen LE, Armand AS, Kinet V, Leptidis S, El Azzouzi H, Salic K, Bourajjaj M, da Silva GJ, Olieslagers S, van der Nagel R, de Weger R, Bitsch N, Kisters N, Seyen S, Morikawa Y, Chanoine C, Heymans S, Volders PG, Thum T, Dimmeler S, Cserjesi P, Eschenhagen T, da Costa Martins PA, De Windt LJ
Publication Title	Nfat and miR-25 cooperate to reactivate the transcription factor Hand2 in heart failure
Publication Status	in revision
Protocol Name	P-MTAB-34191	P-MTAB-34192	P-MTAB-34193	P-MTAB-34194
Protocol Type	growth protocol	treatment protocol	nucleic acid extraction protocol	nucleic acid labeling protocol
Protocol Description	Cardiac RNA was collected from ventricular tissue of 3 tamoxifen-injected Hand2F/F and 3 tamoxifen-injected MCM-Hand2F/F mice (4 weeks after sham or TAC surgery)	Transverse aortic constriction (TAC) or sham surgery was performed on 3 tamoxifen-injected Hand2F/F and 3 tamoxifen-injected MCM-Hand2F/F mice	Cardiac RNA was extracted using Trizol	The assay started with 4Ð8 _g total RNA sample. The detection probes were made by in situ synthesis using photo-generated reagent chemistry. Hybridization used 100 _L 6 _ SSPE buffer (0.90 M NaCl, 60 mM Na2HPO4, 6 mM EDTA, pH 6.8) containing 25% formamide at 34¡C. After RNA hybridization, tag-conjugating Cy3 or Cy5 dyes were circulated through the microfluidic chip for dye staining.
Protocol Term Source REF	EFO	EFO	EFO	EFO
Term Source Name	EFO	ArrayExpress
Term Source File	http://www.ebi.ac.uk/efo	http://www.ebi.ac.uk/arrayexpress
SDRF File	E-MTAB-1821.sdrf.txt
Publication DOI	10.1038/ncb2866