Esrrb, an estrogen‐related receptor involved in early development, pluripotency, and reprogramming

Abstract

Estrogen-related receptor b (Esrrb) is part of a family of three orphan nuclear receptors with broad expression profiles and a generic function in regulating energy metabolism in mammals. However, Esrrb performs specific functions during early mouse development, in pluripotent and multipotent populations of the embryo as well as in primordial germ cells. Moreover, Esrrb also impinges upon the control of self-renewal in embryo-derived stem cells and enhances reprogramming. Here, we review the function of Esrrb with special emphasis on its role in pluripotency. Esrrb activity at crucial regulatory elements of the pluripotency network, coupled with its role as a mitotic bookmarking factor and the ability to reset cellular metabolism, might explain its potent functions in ensuring the stability of pluripotency and driving the late stages of reprogramming. Hence, we argue that Esrrb represents a key addition to the pantheon of transcription factors sustaining pluripotent stem cell identity in mice. Understanding the mechanisms governing the interplay between different estrogen-related receptors (ERRs) and their specificity of action may clarify the role these factors play during preimplantation development and in pluripotent cells in both mouse and humans.

Single cell transcriptional and chromatin accessibility profiling redefine cellular heterogeneity in the adult human kidney

“…9f). ESRRB is an orphan nuclear receptor with a critical role in early development and pluripotency 49,50 and HNF1B is a homeodomain-containing transcription factor that regulates nephrogenesis. Pathogenic germline HNF1B variants are a known cause of autosomal dominant tubulointerstitial kidney disease with hypomagnesemia and hypercalciuria 51 .…”

CTCF confers local nucleosome resiliency after DNA replication and during mitosis

“…2), and the presence of CTCF on newly synthetized chromatin (30), it is likely that CTCF is capable of rapidly rebinding its sites postreplication to efficiently re-establish NDRs and NOAs. We then explored the impact of replication on nucleosome positioning at regions that we previously showed to be organized around the binding motifs of either Esrrb, or Oct4/Sox2, three master TFs of pluripotency (22,31,32). At Esrrb bound regions we observed a prominent NDR centered on the Esrrb motif and two particularly well positioned flanking nucleosomes just after replication.…”

A Novel Approach to Identify Enhancer lincRNAs by Integrating Genome, Epigenome, and Regulatome

“…As a result, 52 TF motifs were enriched in elincRNA TSS intervals, while 90 motifs were enriched in canonical lincRNA TSS intervals with statistical significance (E-value < 0.05) ( Figure 6A). There were four TFs named as NANOG (Loh et al, 2006), POU5F1 (OCT4) (Zhang X. et al, 2008), SOX2 (Kim et al, 2008) and ESRRB (Festuccia et al, 2018), which were the acknowledged proteins or regulators related to cell differentiation and embryonic development, were enriched in the elincRNA TSS regions. NANOG, POU5F1, and SOX2 were the core markers for stem cells, which were essential to maintain mouse embryonic stem cell pluripotency (Loh et al, 2006;Kim et al, 2008).…”