<i>Kcnq1ot1</i> noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1

Mohammad, Faizaan; Mondal, Tanmoy; Guseva, Natalya V.; Pandey, Gaurav Kumar; Kanduri, Chandrasekhar

doi:10.1242/dev.048181

Cited by 257 publications

(209 citation statements)

References 22 publications

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“…This mechanism has been proposed to stimulate gene transcription by preventing access of DNMT1 to loci genome-widely [31]. Our study, in line with another report on Kcnq1ot1 [32], thus expands the concept of DNMT1-interacting RNAs, and suggests that, as opposed to non-poly(A) RNAs, lncRNAs (potentially not just lincRNA-p21 or Kcnq1ot1) promote DNMT1 activity at particular loci.…”

Section: Discussionsupporting

confidence: 88%

The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters

et al. 2014

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Recent studies have boosted our understanding of long noncoding RNAs (lncRNAs) in numerous biological processes, but few have examined their roles in somatic cell reprogramming. Through expression profiling and functional screening, we have identified that the large intergenic noncoding RNA p21 (lincRNA-p21) impairs reprogramming. Notably, lincRNA-p21 is induced by p53 but does not promote apoptosis or cell senescence in reprogramming. Instead, lincRNA-p21 associates with the H3K9 methyltransferase SETDB1 and the maintenance DNA methyltransferase DNMT1, which is facilitated by the RNA-binding protein HNRNPK. Consequently, lincRNA-p21 prevents reprogramming by sustaining H3K9me3 and/or CpG methylation at pluripotency gene promoters. Our results provide insight into the role of lncRNAs in reprogramming and establish a novel link between p53 and heterochromatin regulation.

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Section: Discussionsupporting

confidence: 88%

The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters

et al. 2014

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“…Indeed, preliminary evidence suggests that UV cross-linking assays do not detect the interaction between PRC2 subunits and A-repeat RNA (Maenner et al 2010). The issue of unidentified RBDs extends to other chromatin-modifying factors suggested to interact directly with ncRNAs, specifically G9a , LSD1 (Terranova et al 2008), DNMT1 (Mohammad et al 2010), and the numerous chromatin complexes implicated in lincRNA binding in ES cells (Guttman et al 2011). While it is possible that these factors have all evolved novel RBDs, an alternative explanation is that the assays employed to date do not sufficiently discriminate specific and nonspecific interactions.…”

Section: Discussionmentioning

confidence: 99%

Noncoding RNA and Polycomb recruitment

Brockdorff

2013

RNA

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A plethora of noncoding (nc) RNAs has been revealed through the application of high-throughput analysis of the transcriptome, and this has led to an intensive search for possible biological functions attributable to these transcripts. A major category of functional ncRNAs that has emerged is for those that are implicated in coordinate gene silencing, either in cis or in trans. The archetype for this class is the well-studied long ncRNA Xist which functions in cis to bring about transcriptional silencing of an entire X chromosome in female mammals. An important step in X chromosome inactivation is the recruitment of the Polycomb repressive complex PRC2 that mediates histone H3 lysine 27 methylation, a hallmark of the inactive X chromosome, and recent studies have suggested that this occurs as a consequence of PRC2 interacting directly with Xist RNA. Accordingly, other ncRNAs have been linked to PRC2 targeting either in cis or in trans, and here also the mechanism has been proposed to involve direct interaction between PRC2 proteins and the different ncRNAs. In this review, I discuss the evidence for and against this hypothesis, in the process highlighting alternative models and discussing experiments that, in the future, will help to resolve existing discrepancies.

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“…One way by which Tsix might function to repress Xist is to recruit Dnmt3a activity to methylate and silence the Xist promoter (Sado et al 2006;Sun et al 2006). Similarly, Kcnq1ot1 may recruit Dnmt1 (Mohammad et al 2010).…”

Section: Mechanisms Of Action: Finding Pattern In Chaosmentioning

confidence: 99%

Long Noncoding RNAs: Past, Present, and Future

2013

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Long noncoding RNAs (lncRNAs) have gained widespread attention in recent years as a potentially new and crucial layer of biological regulation. lncRNAs of all kinds have been implicated in a range of developmental processes and diseases, but knowledge of the mechanisms by which they act is still surprisingly limited, and claims that almost the entirety of the mammalian genome is transcribed into functional noncoding transcripts remain controversial. At the same time, a small number of well-studied lncRNAs have given us important clues about the biology of these molecules, and a few key functional and mechanistic themes have begun to emerge, although the robustness of these models and classification schemes remains to be seen. Here, we review the current state of knowledge of the lncRNA field, discussing what is known about the genomic contexts, biological functions, and mechanisms of action of lncRNAs. We also reflect on how the recent interest in lncRNAs is deeply rooted in biology's longstanding concern with the evolution and function of genomes.T HE past several years have witnessed a steep rise of interest in the study of lncRNAs. Almost on a weekly basis, it seems that a new lncRNA is found to be up-or downregulated in a particular disease, or a new class of noncoding transcripts is uncovered by a transcriptomic study, or a new article heralds a paradigm shift that lncRNAs will bring to our understanding of biology. Without a doubt, the advent of sensitive, high-throughput genomic technologies such as microarrays and next-generation sequencing (NGS) has resulted in an unprecedented ability to detect novel transcripts, the vast majority of which seem not to be derived from annotated protein-coding genes. Despite this explosion of data, however, surprisingly little is known about how lncRNAs function, how many different types of lncRNAs exist, or even whether most of them carry biological significance.In this review, we focus on recently discovered lncRNAs of .200 nt, place these new discoveries in historical context, and outline areas where additional work is needed. The review does not cover "classic" ncRNAs such as ribosomal (r) RNAs, ribozymes, transfer (t)RNAs, small nuclear (sn)RNAs, small nucleolar (sno)RNAs, and telomere-associated RNAs (TERC, TERRA); nor does it cover small ncRNAs such as microRNAs (miRNAs), endogenous small interfering (endo-si)RNAs that participate in RNA interference (RNAi), and Piwi-associated (pi)RNAs. We refer readers to the many

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Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1

Cited by 257 publications

References 22 publications

The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters

The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters

Noncoding RNA and Polycomb recruitment

Long Noncoding RNAs: Past, Present, and Future

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