Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression data from Shox2 knockout and wildtype right atria of E11.5 mouse hearts

ABSTRACT: The heartM-bM-^@M-^Ys rhythm is initiated and regulated by a group of specialized cells in the sinoatrial node (SAN), the primary pacemaker of the heart. Abnormalities in the development of the SAN can result in irregular heart rates (arrhythmias). Although several of the critical genes important for SAN formation have been identified, our understanding of the transcriptional network controlling SAN development remains at a relatively early stage. The homeodomain transcription factor Shox2 plays an essential early role in the specification and patterning of the SAN. Here, we compared gene expression levels in the right atria of wildtype and Shox2-/- hearts using microarray experiments to identify Shox2 target genes. Right atria of E11.5 mouse embryos were dissected and genotyped for RNA extraction. RNA from 6 embryos and 2 independent pregnancies was pooled per genotype (Wildtype and Shox2 Knockout) and compared.

ORGANISM(S): Mus musculus

SUBMITTER: Sandra Hoffmann

PROVIDER: E-GEOD-39924 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Islet1 is a direct transcriptional target of the homeodomain transcription factor Shox2 and rescues the Shox2-mediated bradycardia.

Hoffmann Sandra S Berger Ina M IM Glaser Anne A Bacon Claire C Li Li L Gretz Norbert N Steinbeisser Herbert H Rottbauer Wolfgang W Just Steffen S Rappold Gudrun G

Basic research in cardiology 20130301 2

The heart's rhythm is initiated and regulated by a group of specialized cells in the sinoatrial node (SAN), the primary pacemaker of the heart. Abnormalities in the development of the SAN can result in irregular heart rates (arrhythmias). Although several of the critical genes important for SAN formation have been identified, our understanding of the transcriptional network controlling SAN development remains at a relatively early stage. The homeodomain transcription factor Shox2 is involved in ...[more]

PMID: 23455426

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Project description:ChIP-Sequencing on Shox2-HA E12.5 and E13.5 Limb and Palate, as well as Pbx on E12.5 limb . Abstract: Vertebrate appendage patterning is programmed by Hox-TALE factors-bound regulatory elements. However, it remains enigmatic which cell lineages are commissioned by Hox-TALE factors to generate regional specific pattern and whether other Hox-TALE co-factors exist. In this study, we investigated the transcriptional mechanisms controlled by the Shox2 transcriptional regulator in limb patterning. Harnessing an osteogenic lineage-specific Shox2 inactivation approach we show that despite widespread Shox2 expression in multiple cell lineages, lack of the stylopod observed upon Shox2 deficiency is a specific result of Shox2 loss of function in the osteogenic lineage. ChIP-Seq revealed robust interaction of Shox2 with cis-regulatory enhancers clustering around skeletogenic genes that are also bound by Hox-TALE factors, supporting a lineage autonomous function of Shox2 in osteogenic lineage fate determination and skeleton patterning. Pbx ChIP-Seq further allowed the genome-wide identification of cis-regulatory modules exhibiting co-occupancy of Pbx, Meis, and Shox2 transcriptional regulators. Integrative analysis of ChIP-Seq and RNA-Seq data and transgenic enhancer assays indicate that Shox2 patterns the stylopod as a repressor via interaction with enhancers active in the proximal limb mesenchyme and antagonizes the repressive function of TALE factors in osteogenesis. Shox2/TALE For ChIP-Seq, the list of libraries below, including controls, were generated [listed in the format of (antibody)-target-tissue-stage]: (Î±-HA)-Shox2-Limb-E12.5, (Î±-HA)-Shox2-Limb-E13.5, (Î±-HA)-Shox2-Palate-E12.5, (Î±-HA)-Shox2-Limb/Palate-E12.5, (Î±-Pbx)-Pbx-Limb-E12.5, Input (control), (Î±-HA)-Mixed Limb/Palate from Shox2+/+ mice-E12.5 (control). *The attached signal tracks(*.bigwig) were generated by âbdgcmp (MACS2) to filter out background signal(by filtering against the signal track obtained from (Î±-HA)-Mixed Limb/Palate from Shox2+/+ mice-E12.5 (control)) and subsequently convert to bigwig for analysis and visualization.

Dataset Information

Expression data from Shox2 knockout and wildtype right atria of E11.5 mouse hearts

Publications

Islet1 is a direct transcriptional target of the homeodomain transcription factor Shox2 and rescues the Shox2-mediated bradycardia.

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