Your browser doesn't support javascript.
loading
UHRF2 regulates cell cycle, epigenetics and gene expression to control the timing of retinal progenitor and ganglion cell differentiation.
Wang, Xiaohong; Sarver, Aaron L; Han, Qiyuan; Seiler, Christopher L; Xie, Chencheng; Lu, Huarui; Forster, Colleen L; Tretyakova, Natalia Y; Hallstrom, Timothy C.
Afiliação
  • Wang X; Department of Pediatrics, Division of Blood and Marrow Transplantation, 420 Delaware Street S.E., University of Minnesota, Minneapolis, MN 55455, USA.
  • Sarver AL; Institute for Health Informatics, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
  • Han Q; Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
  • Seiler CL; Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
  • Xie C; Department of Pediatrics, Division of Blood and Marrow Transplantation, 420 Delaware Street S.E., University of Minnesota, Minneapolis, MN 55455, USA.
  • Lu H; Department of Pediatrics, Division of Blood and Marrow Transplantation, 420 Delaware Street S.E., University of Minnesota, Minneapolis, MN 55455, USA.
  • Forster CL; BioNet, Academic Health Center, University of Minnesota, Minneapolis, MN 55455, USA.
  • Tretyakova NY; Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
  • Hallstrom TC; Department of Pediatrics, Division of Blood and Marrow Transplantation, 420 Delaware Street S.E., University of Minnesota, Minneapolis, MN 55455, USA.
Development ; 149(6)2022 03 15.
Article em En | MEDLINE | ID: mdl-35285483
Ubiquitin-like, containing PHD and RING finger domains 2 (UHRF2) regulates cell cycle and binds 5-hydroxymethylcytosine (5hmC) to promote completion of DNA demethylation. Uhrf2-/- mice are without gross phenotypic defects; however, the cell cycle and epigenetic regulatory functions of Uhrf2 during retinal tissue development are unclear. Retinal progenitor cells (RPCs) produce all retinal neurons and Müller glia in a predictable sequence controlled by the complex interplay between extrinsic signaling, cell cycle, epigenetic changes and cell-specific transcription factor activation. In this study, we find that UHRF2 accumulates in RPCs, and its conditional deletion from mouse RPCs reduced 5hmC, altered gene expressions and disrupted retinal cell proliferation and differentiation. Retinal ganglion cells were overproduced in Uhrf2-deficient retinae at the expense of VSX2+ RPCs. Most other cell types were transiently delayed in differentiation. Expression of each member of the Tet3/Uhrf2/Tdg active demethylation pathway was reduced in Uhrf2-deficient retinae, consistent with locally reduced 5hmC in their gene bodies. This study highlights a novel role of UHRF2 in controlling the transition from RPCs to differentiated cell by regulating cell cycle, epigenetic and gene expression decisions.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Retina / Ubiquitina-Proteína Ligases / Epigênese Genética Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Development Assunto da revista: BIOLOGIA / EMBRIOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Retina / Ubiquitina-Proteína Ligases / Epigênese Genética Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Development Assunto da revista: BIOLOGIA / EMBRIOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido