The variant Polycomb Repressor Complex 1 component PCGF1 interacts with a pluripotency sub-network that includes DPPA4, a regulator of embryogenesis

Abstract

The regulation of gene expression through epigenetic mechanisms operates at several levels. These include modification of DNA itself, modification of the histone proteins in contact with DNA, as well as higher order regulation involving 'remodelling' and three-dimensional rearrangement of chromosomes to increase or decrease accessibility to the DNA by transcription factors 1 . Many of these changes are mediated by large heteromeric protein complexes possessing multiple activities that ensure that specific epigenetic changes occur at particular genes at the correct time.One family of such complexes are known as Polycomb Repressive Complexes (PRC) 2,3 . The genes encoding components of these complexes were originally isolated in genetic screens of Drosophila, where mutants display a variety of developmental phenotypes, suggesting a critical role for Polycomb genes in the regulating of genes involved in cell fate determination and differentiation 4,5 . Later biochemical work established that Polycomb function was mediated by two classes of multi-protein enzymatic complexes (PRC1 and PRC2) whose central catalytic functions include histone post-translational modification activities (i.e. ubiquitin ligase and methyltransferase activity respectively). The catalytic core of PRC1 in humans is a heterodimer comprising either of two related E3 ubiquitin ligases, RING1 (RING1A) or RNF2 (RING1B) and one of six PCGF orthologs [6][7][8][9][10] .

The Construction and Identification of Induced Pluripotent Stem Cells Derived from Acute Myelogenous Leukemia Cells

“…DNMT3b is a type of methyltransferase that mediates DNA methylation and plays an important role in the growth and development of embryonic stem cells [36]. DPPA2 and DPPA4 are both recently identified specific marker genes in embryonic stem cells, wherein DPPA2 plays an important role in maintaining the undifferentiated state and proliferation of embryonic stem cells, and DPPA4 is involved in regulating the differentiation of embryonic stem cells into ectodermal cells [37, 38]. Therefore, because of the important roles played by the above genes in the differentiation and pluripotency of adult stem cells, we can speculate that the iPSCs exhibit the characteristics of stem cells in all respects.…”

From Flies to Mice: The Emerging Role of Non-Canonical PRC1 Members in Mammalian Development

“…PCGF1 directly interacts with BCOR, RNF2 and RYBP [52,107,269]. Knockdown of Pcgf1 in HeLa and embryonal carcinoma cell line NT2/D1 results in significant reduction of H2A ubiquitination and DNA demethylation [270].…”

“…The different PCGF subunits recruit diverse set of associated proteins. A plethora (83) of new ncPRC1.1 interacting proteins were identified linking non-canonical Polycomb repression to cell cycle regulation and pluripotency [269]. Consequently, different ncPRC1 complexes have altered gene targets and profoundly different function.…”

“…Highly sensitive affinity purification mass spectrometry (MS) approaches revealed a whole new set of interactor proteins both from Drosophila embryos [355] and from mammalian cells [51,179,269]. The identification of the new players further increases the diversity of the targeting and interaction possibilities of the Polycomb system.…”

Genomic functions of developmental pluripotency associated factor 4 (Dppa4) in pluripotent stem cells and cancer

“…Dppa4 mainly associates with active, euchromatic domains as assessed by cytostaining (Masaki et al, 2007), but it is also a member of a non-canonical Polycomb repressive complex (Oliviero et al, 2015), and it represses transcription in GAL4 assays in vitro (Tung et al, 2013). Dppa4 contains an N-terminal SAP (SAF-A/B, Acinus and PIAS) domain, which is thought to mediate Dppa4 DNA binding, but it also associates with histone H3 through its C-terminal domain (Masaki et al, 2010).…”