lncRNA Panct1 Maintains Mouse Embryonic Stem Cell Identity by Regulating TOBF1 Recruitment to Oct-Sox Sequences in Early G1

Abstract

Long noncoding RNAs (lncRNAs) have been implicated in diverse biological processes, including embryonic stem cell (ESC) maintenance. However, their functional mechanisms remain largely undefined. Here, we show that the lncRNA Panct1 regulates the transient recruitment of a putative X-chromosome-encoded protein A830080D01Rik, hereafter referred to as transient octamer binding factor 1 (TOBF1), to genomic sites resembling the canonical Oct-Sox motif. TOBF1 physically interacts with Panct1 and exhibits a cell-cycle-specific punctate localization in ESCs. At the chromatin level, this correlates with its recruitment to promoters of pluripotency genes. Strikingly, mutating an octamer-like motif in Panct1 RNA abrogates the strength of TOBF1 localization and recruitment to its targets. Taken together, our data reveal a tightly controlled spatial and temporal pattern of lncRNA-mediated gene regulation in a cell-cycle-dependent manner and suggest that lncRNAs might function as barcodes for identifying genomic addresses for maintaining cellular states.

Genome-Scale CRISPR Screening reveals novel factors regulating Wnt-dependent regeneration of mouse gastric organoids

“…However, our IWP2 treatment results ( Supplementary Figure 6c) indicate that these upregulated Wnts may not be suffficient to maintain gastric regeneration. It has been reported that Bclaf3 binds to the Oct-Sox binding motif and is necessary to maintain pluripotency of mouse embryonic stem cells (mESCs) (24). In contrast to this report, we find that Bclaf3 expression is present in non-stem cells and may induce differentiation in gastric glands by supressing Wnt signalling and Reg family genes.…”

Gas5 is an essential lncRNA regulator for self-renewal and pluripotency of mouse embryonic stem cells and induced pluripotent stem cells

“…ESCs are an excellent in vitro model for studying the role of lncRNAs in pluripotent cells and cellular differentiation [ 13 , 14 ]. To identify lncRNAs participating in mESC pluripotency and lineage differentiation, we analyzed the transcriptome of mESCs during differentiation [ 15 ].…”

X Chromosome Dosage Modulates Multiple Molecular and Cellular Properties of Mouse Pluripotent Stem Cells Independently of Global DNA Methylation Levels

“…Therefore, identifying additional X-linked regulators that mediate the effects X-dosage in pluripotent stem cells requires future investigations [10]. An interesting additional candidate is the recently-identified X-linked transient octamer binding factor 1 (TOBF1) [53], since it was shown to sustain pluripotency. It is also possible that other regulators of the Erk pathway are involved.…”