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| Status |
Public on Mar 15, 2012 |
| Title |
Genome-wide profiling of E12.5 cardiomyocytes RNA expression in both heterozygous control and mutant |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Congenital heart disease is among the most frequent major birth defects. Epigenetic marks are crucial for organogenesis, but their role in heart development is poorly understood. Polycomb Repressive Complex 2 (PRC2) trimethylates histone H3 at lysine 27, establishing H3K27me3 repressive epigenetic marks that promote tissue-specific differentiation by silencing ectopic gene programs. We studied the function of the catalytic subunit of PRC2, EZH2, in murine heart development. Early EZH2 inactivation by Nkx2-5Cre caused lethal congenital heart malformations, but slightly later EZH2 inactivation by cTNT-Cre did not. To study how the cardiomyocytes gene expression program is properly established in the early heart development, we combined the technologies of RNA sequencing and chromatin immunoprecipitation sequencing to identify the functional target genes directly repressed by EZH2. Intriguingly, these were enriched for transcriptional regulators of non-cardiac expression programs, such as transcription factors that regulate neuronal (Pax6) and cardiac progenitor genes (Isl1 and Six1). EZH2 was also required to maintain spatiotemporal regulation of cardiac gene expression, as Hcn4, Mlc2a, and Bmp10 were inappropriately upregulated in ventricular RNA. Furthermore, EZH2 was required for normal cardiomyocyte proliferation, establishing H3K27me3 epigenetic marks at cell cycle inhibitors Ink4a/b and repressing their expression. Our study reveals a previously undescribed role of EZH2 in regulating heart formation and shows that perturbation of the epigenetic landscape early cardiogenesis has sustained disruptive effects at later developmental stages.
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| Overall design |
8 E12.5 heart apex were used for RNA preparation each group.
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| Contributor(s) |
He A, Pu WT |
| Citation(s) |
22158708 |
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| Submission date |
Jun 15, 2011 |
| Last update date |
Mar 19, 2019 |
| Contact name |
Michael Hsing |
| Organization name |
Children's Hospital Boston
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| Department |
Cardiology
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| Street address |
300 Longwood Ave.
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE29997 |
Ezh2 and H3K27me3 in cardiomyocytes |
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| Relations |
| BioProject |
PRJNA155341 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE29992_Het1_KO2_expr.txt.gz |
1.4 Mb |
(ftp)(http) |
TXT |
| GSE29992_RAW.tar |
1.8 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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