Retroposition and evolution of the DNA-binding motifs of YY1, YY2 and REX1

Abstract

YY1 is a DNA-binding transcription factor found in both vertebrates and invertebrates. Database searches identified 62 YY1 related sequences from all the available genome sequences ranging from flying insects to human. These sequences are characterized by high levels of sequence conservation, ranging from 66% to 100% similarity, in the zinc finger DNA-binding domain of the predicted proteins. Phylogenetic analyses uncovered duplication events of YY1 in several different lineages, including flies, fish and mammals. Retroposition is responsible for generating one duplicate in flies, PHOL from PHO, and two duplicates in placental mammals, YY2 and Reduced Expression 1 (REX1) from YY1. DNA-binding motif studies have demonstrated that YY2 still binds to the same consensus sequence as YY1 but with much lower affinity. In contrast, REX1 binds to DNA motifs divergent from YY1, but the binding motifs of REX1 and YY1 share some similarity at their core regions (5′-CCAT-3′). This suggests that the two duplicates, YY2 and REX1, although generated through similar retroposition events have undergone different selection schemes to adapt to new roles in placental mammals. Overall, the conservation of YY2 and REX1 in all placental mammals predicts that each duplicate has co-evolved with some unique features of eutherian mammals.

Control of embryonic stem cell self-renewal and differentiation via coordinated alternative splicing and translation of YY2

“…Nearly half of the peaks contained the consensus YY1-binding motif (Fig. 3C), as is consistent with a similar sequence preference for YY1 and YY2 (21,22). Motif distribution across binding peaks revealed enrichment for the known consensus YY1-binding motif directly at YY2 peak centers (Fig.…”

“…YY1 is a pleiotropic transcription factor that regulates diverse cellular processes and plays a critical role in early embryonic development, ESC biology, and reprogramming (25)(26)(27). Although the N-terminal domains of YY1 and YY2 differ significantly, the C-terminal DNA-binding domain of YY1 is highly conserved in Rex1 and YY2 (22), suggesting that YY2 may play an important role in the regulation of gene expression in mESCs. Although there is no significant change in the level of Yy2 mRNA in DKO mESCs compared with WT cells (Fig.…”

Timing is everything

“…78 In mouse Rex1 null mutants, the DNA methylation at the differentially methylated regions of several imprinted loci is disrupted in adult tissues despite the fact that Rex1 is only expressed very early in development. 79 …”

Functional Analysis ofRex1During Preimplantation Development

“…Rex1 was generated by duplication from Yy1 by retrotransposition, displays significant similarity to the Yy1 transcription factor in the zinc-finger domains, and is present exclusively in eutherian mammals [21]. Rex1 was first discovered as a result of its specific expression in pluripotent F9 embryonal carcinoma cells [22].…”