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Uhrf1 and Dnmt1 are required for development and maintenance of the zebrafish lens.

Developmental biology | Feb 1, 2011

http://www.ncbi.nlm.nih.gov/pubmed/21126517

DNA methylation is one of the key mechanisms underlying the epigenetic regulation of gene expression. During DNA replication, the methylation pattern of the parent strand is maintained on the replicated strand through the action of Dnmt1 (DNA Methyltransferase 1). In mammals, Dnmt1 is recruited to hemimethylated replication foci by Uhrf1 (Ubiquitin-like, Containing PHD and RING Finger Domains 1). Here we show that Uhrf1 is required for DNA methylation in vivo during zebrafish embryogenesis. Due in part to the early embryonic lethality of Dnmt1 and Uhrf1 knockout mice, roles for these proteins during lens development have yet to be reported. We show that zebrafish mutants in uhrf1 and dnmt1 have defects in lens development and maintenance. uhrf1 and dnmt1 are expressed in the lens epithelium, and in the absence of Uhrf1 or of catalytically active Dnmt1, lens epithelial cells have altered gene expression and reduced proliferation in both mutant backgrounds. This is correlated with a wave of apoptosis in the epithelial layer, which is followed by apoptosis and unraveling of secondary lens fibers. Despite these disruptions in the lens fiber region, lens fibers express appropriate differentiation markers. The results of lens transplant experiments demonstrate that Uhrf1 and Dnmt1 functions are required lens-autonomously, but perhaps not cell-autonomously, during lens development in zebrafish. These data provide the first evidence that Uhrf1 and Dnmt1 function is required for vertebrate lens development and maintenance.

Pubmed ID: 21126517 RIS Download

Mesh terms: Alleles | Animals | Apoptosis | Cell Differentiation | DNA (Cytosine-5-)-Methyltransferase | DNA Methylation | Epigenesis, Genetic | Epithelium | Gene Expression Regulation, Developmental | Gene Expression Regulation, Plant | Lens, Crystalline | Mutation | Retina | Trans-Activators | Zebrafish | Zebrafish Proteins

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Associated grants

  • Agency: NEI NIH HHS, Id: F32 EY020745
  • Agency: NEI NIH HHS, Id: F32 EY020745-02
  • Agency: NEI NIH HHS, Id: F32-EY020745
  • Agency: NCRR NIH HHS, Id: P40 RR012546
  • Agency: NIDCR NIH HHS, Id: R00 DE018088
  • Agency: NIDCR NIH HHS, Id: R00 DE018088-05
  • Agency: NIDCR NIH HHS, Id: R00-DE018088
  • Agency: NIDDK NIH HHS, Id: R01 DK060322
  • Agency: NIDDK NIH HHS, Id: R01 DK060322-10
  • Agency: NIDDK NIH HHS, Id: R01 DK075032
  • Agency: NIDDK NIH HHS, Id: R01 DK075032-05
  • Agency: NEI NIH HHS, Id: R01 EY018005
  • Agency: NEI NIH HHS, Id: R01 EY018005-03
  • Agency: NIDDK NIH HHS, Id: R01-DK075032
  • Agency: NIDDK NIH HHS, Id: R01-DK60322
  • Agency: NEI NIH HHS, Id: R01-EY18005

ZFIN (Data, Gene Expression)

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