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Genetic dissection of a super enhancer controlling the Nppa-Nppb cluster in the heart of RE3 mutants

ABSTRACT: High-resolution chromosome conformation capture-sequencing of RE3 homozygous mutants

ORGANISM(S): Mus musculus

PROVIDER: GSE155140 | GEO | 2021/07/30

REPOSITORIES: GEO

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Genetic dissection of a super enhancer controlling the Nppa-Nppb cluster in the heart after cardiac stress

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Identification of a regulatory domain controlling the Nppa-Nppb gene cluster during heart development and stress

Project description:The paralogous genes Nppa and Nppb are organized in an evolutionary conserved cluster and are a valuable model to study coregulation and regulatory landscape organization during heart development and disease. Here, we analyzed the chromatin conformation, epigenetic status and enhancer potential of sequences of the Nppa-Nppb cluster in vivo. Our data indicate that the regulatory landscape of the cluster is present within a 60 kbp domain centered around Nppb. Both promoters and several potential regulatory elements interact with each other in a similar manner in different tissues and developmental stages. The distribution of H3K27ac and the association of Pol2 across the locus changed during cardiac hypertrophy, revealing their potential involvement in stress-mediated gene regulation. In summary, the developmental regulation and stress-response of the Nppa-Nppb cluster involve the concerted action of multiple enhancers and epigenetic changes distributed across a structurally rigid regulatory domain. We have used 4C-seq on several viewpoints around the Nppa-Nppb gene cluster in the heart and liver samples to investigate the role of chromatin conformation on regulation of Nppa and Nppb expression during heart development and disease.

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Genetic dissection of a super enhancer controlling the Nppa-Nppb cluster in the heart

Project description:Genetic dissection of a super enhancer controlling the Nppa-Nppb cluster in the heart

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Genetic dissection of a super enhancer controlling the Nppa-Nppb cluster in the heart of RE3 mutants

Project description:Genetic dissection of a super enhancer controlling the Nppa-Nppb cluster in the heart of RE3 mutants

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Identification of a regulatory domain controlling the Nppa-Nppb gene cluster during heart development and stress

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Genetic dissection of a super enhancer controlling the Nppa-Nppb cluster in the heart after cardiac stress

Project description:Genetic dissection of a super enhancer controlling the Nppa-Nppb cluster in the heart after cardiac stress

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Structure and function of the Nppa-Nppb cluster locus during heart development and disease.

Project description:Atrial natriuretic factor and brain natriuretic peptide are two important biomarkers in clinical cardiology. These two natriuretic peptide hormones are encoded by the paralogous genes Nppa and Nppb, which are evolutionary conserved. Both genes are predominantly expressed by the heart muscle during the embryonic and fetal stages, and in particular Nppa expression is strongly reduced in the ventricles after birth. Upon cardiac stress, Nppa and Nppb are strongly upregulated in the ventricular myocardium. Much is known about the molecular and physiological ques inducing Nppa and Nppb expression; however, the transcriptional regulatory mechanisms of the Nppa-Nppb cluster in vivo has proven to be quite complex and is not well understood. In this review, we will provide recent insights into the dynamic and complex regulation of Nppa and Nppb during heart development and hypertrophy, and the association of this gene cluster with the cardiomyocyte-intrinsic program of heart regeneration.

| S-EPMC5852170 | biostudies-literature

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