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

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  • Additional Information
    • Source:
      Publisher: Company Of Biologists Limited Country of Publication: England NLM ID: 8701744 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-9129 (Electronic) Linking ISSN: 09501991 NLM ISO Abbreviation: Development Subsets: MEDLINE
    • Publication Information:
      Publication: Cambridge Eng : Company Of Biologists Limited
      Original Publication: [Cambridge] : Company of Biologists, [c1987-
    • Subject Terms:
      Multigene Family*; Heart/*embryology ; Natriuretic Peptide, C-Type/*metabolism ; Protein Precursors/*metabolism ; Receptors, Atrial Natriuretic Factor/*metabolism ; Stress, Physiological/*genetics; Acetylation ; Animals ; Atrial Natriuretic Factor ; Enhancer Elements, Genetic ; Epigenesis, Genetic ; Gene Expression Regulation, Developmental ; Genetic Loci ; Histones/metabolism ; Lysine/metabolism ; Mice ; Models, Biological ; Natriuretic Peptide, C-Type/genetics ; Promoter Regions, Genetic ; Protein Precursors/genetics ; RNA Polymerase II/metabolism ; Receptors, Atrial Natriuretic Factor/genetics
    • Abstract:
      The paralogous genes Nppa and Nppb are organized in an evolutionarily conserved cluster and provide a valuable model for studying co-regulation 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-kb 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. Functional analysis of double-reporter transgenic mice revealed that Nppa and Nppb share developmental, but not stress-response, enhancers, responsible for their co-regulation. Moreover, the Nppb promoter was required, but not sufficient, for hypertrophy-induced Nppa expression. 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.
      (© 2016. Published by The Company of Biologists Ltd.)
    • Contributed Indexing:
      Keywords: Atrial and brain natriuretic peptide; Chromosome conformation; Epigenetics; Heart development; Hypertrophy; Mouse
    • Accession Number:
      0 (Histones)
      0 (Nppa protein, mouse)
      0 (Protein Precursors)
      127869-51-6 (Natriuretic Peptide, C-Type)
      85637-73-6 (Atrial Natriuretic Factor)
      EC 2.7.7.- (RNA Polymerase II)
      EC 4.6.1.2 (Receptors, Atrial Natriuretic Factor)
      EC 4.6.1.2 (atrial natriuretic factor receptor B)
      K3Z4F929H6 (Lysine)
    • Publication Date:
      Date Created: 20160407 Date Completed: 20170905 Latest Revision: 20201209
    • Publication Date:
      20221213
    • Accession Number:
      10.1242/dev.132019
    • Accession Number:
      27048739