Abstract
Long noncoding RNAs (lncRNAs) have been implicated in diverse biological processes including embryonic stem (ES) cell 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 ES cells. At the chromatin level, this correlates with its recruitment to promoters of pluripotency genes. Strikingly, mutating an octamer-like motif in Panct1 mRNA 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.
Highlights
Long noncoding RNAs are known to play diverse functional roles in a multitude of different biological pathways including disease progression, developmental regulation, and maintenance of cellular states (Engreitz et al, 2016). lncRNAmediated regulation is a vital component of a cell’s intrinsic ability to divide, proliferate, and differentiate, with lncRNA perturbations frequently giving rise to phenotypic alterations to normal cellular behavior (Ulitsky and Bartel, 2013)
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 embryonic stem cell (ESC)
Summary
Long noncoding RNAs (lncRNAs) are known to play diverse functional roles in a multitude of different biological pathways including disease progression, developmental regulation, and maintenance of cellular states (Engreitz et al, 2016). lncRNAmediated regulation is a vital component of a cell’s intrinsic ability to divide, proliferate, and differentiate, with lncRNA perturbations frequently giving rise to phenotypic alterations to normal cellular behavior (Ulitsky and Bartel, 2013). LncRNAmediated regulation is a vital component of a cell’s intrinsic ability to divide, proliferate, and differentiate, with lncRNA perturbations frequently giving rise to phenotypic alterations to normal cellular behavior (Ulitsky and Bartel, 2013). This is true in the case of embryonic stem cells (ESCs), where subtle changes in lncRNA expression can lead to a loss of self-renewal and differentiation (Martello and Smith, 2014; Young, 2011). We previously identified an X-chromosome-associated intronic lncRNA termed Panct from an RNAi screen that affected Pou5f1 ( known as Oct4) expression (Chakraborty et al, 2012). We present its molecular characterization and show that Panct regulates and interacts with the previously uncharacterized protein A830080D01Rik, hereafter referred to as transient octamer binding factor 1 (TOBF1), to influence mouse ESC fate
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