PUBLICATION

Zebrafish macroH2A variants have distinct embryo localization and function

Authors
Gonzalez-Munoz, E., Arboleda-Estudillo, Y., Chanumolu, S.K., Otu, H.H., Cibelli, J.B.
ID
ZDB-PUB-190616-1
Date
2019
Source
Scientific Reports   9: 8632 (Journal)
Registered Authors
Arboleda-Estudillo, Yoana, Gonzalez-Muñoz, Elena
Keywords
none
MeSH Terms
  • Zebrafish/embryology*
  • Zebrafish/genetics*
  • Green Fluorescent Proteins/metabolism
  • Embryo, Nonmammalian/metabolism*
  • Genetic Variation*
  • Time Factors
  • DNA/metabolism
  • Promoter Regions, Genetic
  • Animals
  • Embryonic Development/genetics
  • Heterochromatin/metabolism
  • Histones/genetics*
  • Gene Expression Regulation, Developmental
  • Protein Isoforms/genetics
  • Protein Isoforms/metabolism
(all 15)
PubMed
31201343 Full text @ Sci. Rep.
Abstract
Mouse and cell-based studies have shown that macroH2A histone variants predominantly associate with heterochromatin. Functional studies found that macroH2As are involved in gene repression, inhibiting the acquisition of pluripotency and preserving cell differentiation. However, only a few studies have analysed the role of macroH2A during early embryo development. We report the development of transgenic zebrafish lines expressing macroH2A isoforms (mH2A1 and mH2A2) fusion proteins (with GFP) under identified endogenous promoters. We found that mH2A1 and mH2A2 have different spatial and temporal expression patterns during embryonic development. mH2A1 is expressed mostly in the extraembryonic Yolk Syncytial Layer (YSL) starting before shield stage and decreasing once morphogenesis is completed. mH2A2 expression lags behind mH2A1, becoming evident at 24 hpf, within the whole body of the embryo proper. Our ChIP-seq analysis showed that mH2A1 and mH2A2 bind to different DNA regions, changing dramatically after gastrulation. We further analysed RNA-seq data and showed that there is not a general/unspecific repressing function of mH2A1 or mH2A2 associated with heterochromatin but a fine regulation depending on cell types and stage of development. mH2A1 downregulates DNA expression in specific cells and embryo stages and its effect is independent of heterochromatin formation but it is correlated with nucleus quiescence instead. Whereas mH2A2 DNA association correlates with upregulation of differentially expressed genes between 75% epiboly and 24 hpf stages. Our data provide information for underlying molecules that participate in crucial early developmental events, and open new venues to explore mH2A related mechanisms that involve cell proliferation, differentiation, migration and metabolism.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
zf2236TgTransgenic Insertion
    zf2237TgTransgenic Insertion
      zf2238TgTransgenic Insertion
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        macroh2a1MO1-macroh2a1MRPHLNO
        macroh2a2MO2-macroh2a2MRPHLNO
        tp53MO4-tp53MRPHLNO
        1 - 3 of 3
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        Fish
        No data available
        Antibodies
        No data available
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        EGFPEFGEGFP
        1 - 1 of 1
        Show
        Mapping
        No data available
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        Citation
        Gonzalez-Munoz, E., Arboleda-Estudillo, Y., Chanumolu, S.K., Otu, H.H., Cibelli, J.B. (2019) Zebrafish macroH2A variants have distinct embryo localization and function. Scientific Reports. 9:8632.