Evolving Role of RING1 and YY1 Binding Protein in the Regulation of Germ-Cell-Specific Transcription

Genes (Basel). 2019 Nov 19;10(11):941. doi: 10.3390/genes10110941.

Abstract

Separation of germline cells from somatic lineages is one of the earliest decisions of embryogenesis. Genes expressed in germline cells include apoptotic and meiotic factors, which are not transcribed in the soma normally, but a number of testis-specific genes are active in numerous cancer types. During germ cell development, germ-cell-specific genes can be regulated by specific transcription factors, retinoic acid signaling and multimeric protein complexes. Non-canonical polycomb repressive complexes, like ncPRC1.6, play a critical role in the regulation of the activity of germ-cell-specific genes. RING1 and YY1 binding protein (RYBP) is one of the core members of the ncPRC1.6. Surprisingly, the role of Rybp in germ cell differentiation has not been defined yet. This review is focusing on the possible role of Rybp in this process. By analyzing whole-genome transcriptome alterations of the Rybp-/- embryonic stem (ES) cells and correlating this data with experimentally identified binding sites of ncPRC1.6 subunits and retinoic acid receptors in ES cells, we propose a model how germ-cell-specific transcription can be governed by an RYBP centered regulatory network, underlining the possible role of RYBP in germ cell differentiation and tumorigenesis.

Keywords: Nanog; Oct4; Rybp; Sall4; apoptosis; germ cell differentiation; meiosis; ncPRC1; polycomb repression; retinoic acid; transcriptional regulation; transcriptome; ubiquitylation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Binding Sites
  • Carcinogenesis / genetics
  • Cell Differentiation / genetics
  • Cell Line
  • Cell Lineage / genetics
  • Embryonic Stem Cells / metabolism*
  • Embryonic Stem Cells / pathology
  • Gene Expression Regulation, Developmental*
  • Gene Expression Regulation, Neoplastic
  • Gene Knockout Techniques
  • Gene Regulatory Networks
  • Humans
  • Models, Genetic*
  • Neoplasms, Germ Cell and Embryonal / genetics
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Polycomb Repressive Complex 1 / metabolism
  • RNA-Seq
  • Receptors, Retinoic Acid / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transcription, Genetic*

Substances

  • Receptors, Retinoic Acid
  • Repressor Proteins
  • Polycomb Repressive Complex 1