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

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.

The Polycomb Orthologues in Teleost Fishes and Their Expression in the Zebrafish Model

“…The hypothesis of a Pcgf redundancy in teleost fishes is in agreement with the absence of certain pcgf gene members in the genome of several fish species including zebrafish and the medaka [37] and with the fact that pcgf1 zebrafish mutants are viable and fertile [78]. However, the situation might be different in mammals where PCGF functions are definitively not redundant [79,80]. Surprisingly, although about 15% to 20% of the ohnologues were retained as pairs after the TGD in teleost [9], the maintenance of two ohnologues is globally a general characteristic of all cbx family members.…”

Evaluation of Male Fertility-Associated Loci in a European Population of Patients with Severe Spermatogenic Impairment

“…The functional annotations of this SNP are consistent with this idea. TUSC1 -rs10966811 is located in a target sequence for YY1, a transcription factor that has been reported to play a major role in spermatogonial stem cell (SSC) maturation, being expressed in spermatocytes, spermatogonia, and spermatids, but not in mature spermatozoa [ 33 , 34 ]. The TUSC1 -rs10966811 polymorphism represents a crucial position in the consensus sequence recognized by YY1, and the presence of the G allele correlates with a drastic decrease of the binding affinity ( Table S8 and Figure S6 ).…”

“…Such deregulation could be a consequence of an alteration of a binding protein motif by USP8 -rs7174015*A or any of its proxies ( Table S8 and Figure S7 ). In this context, a proxy of this SNP, rs12593481, is located within a consensus sequence for PAX5 and YY1, which are relevant transcription factors in the regulation of the spermatogenic process [ 33 , 34 , 44 ].…”

RYBP is important for cardiac progenitor cell development and sarcomere formation

“…The precise mechanism by which RYBP exerts its functions throughout development is still not thoroughly known. The activity of RYBP containing ncPRC1 complexes is strongly influenced by their subunit composition and stoichiometry [9,37]. ncPRC1s contain RING finger protein 1 (RING1 also known as RING1A), RNF2, Polycomb Group Ring Fingers (PCGFs) and RYBP or YY1 associated factor 2 (YAF2) as the core subunits instead of Chromobox (CBX) and Histone phosphorylation (HPH) subunits of PRC1s.…”

“…It is possible that RYBP could either act via polycomb dependent or polycomb independent manner, regulating key lineage determinant factors which are critical for progenitor formation in wild type conditions. Moreover, RYBP can perform more than one function being a moonlighting protein, and member of several multiprotein complexes besides ncPRC1s [9,37]. This brings up the possibility that RYBP can also function as a part of other multimeric protein complexes other than ncPRC1s and regulate cardiac progenitor as well as sarcomere formation consequently (Fig 7).…”