Jpx RNA Activates Xist by Evicting CTCF

Sun, Sha; Rosario, Brian C. Del; Szántó, Attila; Ogawa, Yasushi; Jeon, Yongho; Lee, Jeannie T.

doi:10.1016/j.cell.2013.05.028

Cited by 282 publications

(319 citation statements)

References 55 publications

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“…Indeed, CTCF has been implicated in establishing and maintaining euchromatic chromatin loop domains or 'insulated neighborhoods' in autosomes (Filipowicz et al, 2005;Sun et al, 2013;Dowen et al, 2014), and in providing an insulator function to partition euchromatic and heterochromatic regions of chromosomes (Wendt et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Escape of X-linked miRNA genes from meiotic sex chromosome inactivation

et al. 2015

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Past studies have indicated that transcription of all X-linked genes is repressed by meiotic sex chromosome inactivation (MSCI) during the meiotic phase of spermatogenesis in mammals. However, more recent studies have shown an increase in steady-state levels of certain X-linked miRNAs in pachytene spermatocytes, suggesting that either synthesis of these miRNAs increases or that degradation of these miRNAs decreases dramatically in these cells. To distinguish between these possibilities, we performed RNA-FISH to detect nascent transcripts from multiple miRNA genes in various spermatogenic cell types. Our results show definitively that Type I X-linked miRNA genes are subject to MSCI, as are all or most X-linked mRNA genes, whereas Type II and III X-linked miRNA genes escape MSCI by continuing ongoing, active transcription in primary spermatocytes. We corroborated these results by co-localization of RNA-FISH signals with both a corresponding DNA-FISH signal and an immunofluorescence signal for RNA polymerase II. We also found that X-linked miRNA genes that escape MSCI locate non-randomly to the periphery of the XY body, whereas genes that are subject to MSCI remain located within the XY body in pachytene spermatocytes, suggesting that the mechanism of escape of X-linked miRNA genes from MSCI involves their relocation to a position outside of the repressive chromatin domain associated with the XY body. The fact that Type II and III X-linked miRNA genes escape MSCI suggests an immediacy of function of the encoded miRNAs specifically required during the meiotic stages of spermatogenesis.

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Section: Discussionmentioning

confidence: 99%

Escape of X-linked miRNA genes from meiotic sex chromosome inactivation

et al. 2015

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“…LncRNAs may function by physically interacting with transcriptional factors, histone regulators, and other cellular factors (20)(21)(22)(23). To explore the mechanism of GClnc1-mediated carcinogenesis in gastric cancer, we sought to identify intracellular GClnc1-binding factors using an unbiased approach.…”

Section: Gclnc1 Interacts With Wdr5 and Kat2a Epigenetic Modifi Catiomentioning

confidence: 99%

LncRNA GClnc1 Promotes Gastric Carcinogenesis and May Act as a Modular Scaffold of WDR5 and KAT2A Complexes to Specify the Histone Modification Pattern

et al. 2016

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Long noncoding RNAs (lncRNA) play a role in carcinogenesis. However, the function of lncRNAs in human gastric cancer remains largely unknown. In this study, we identifi ed a novel lncRNA, GClnc1, which was upregulated and associated with tumorigenesis, tumor size, metastasis, and poor prognosis in gastric cancer. GClnc1 affected gastric cancer cell proliferation, invasiveness, and metastasis in multiple gastric cancer models. Mechanistically, GClnc1 bound WDR5 (a key component of histone methyltransferase complex) and KAT2A histone acetyltransferase, acted as a modular scaffold of WDR5 and KAT2A complexes, coordinated their localization, specifi ed the histone modifi cation pattern on the target genes, including SOD2 , and consequently altered gastric cancer cell biology. Thus, GClnc1 is mechanistically, functionally, and clinically oncogenic in gastric cancer. Targeting GClnc1 and its pathway may be meaningful for treating patients with gastric cancer. SIGNIFICANCE:This report documents a novel lncRNA, GClnc1, which may act as a scaffold to recruit the WDR5 and KAT2A complex and modify the transcription of target genes. This study reveals that GClnc1 is an oncogenic lncRNA in human gastric cancer. Cancer Discov; 6(7); 784-801.

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“…Prior to XCI, CTCF normally inhibits the Xist expression. However, in the absence of CTCF, Jpx activates the Xist promoter [33]. In summary, these results broaden the classic understanding of how genes or chromosomes are regulated.…”

Section: Lncrnas Influence Gene and Genome Regulationmentioning

confidence: 77%

“…½-sbsRNA mRNA degradation; transactivation of STAU1 for mRNA binding [53] Air chromatin remodeling; mono-allelic expression; imprinting and silencing of gene loci in cis in murine placenta [35] Braveheart determination of the cardial lineage in mouse [55] EGO regulation of eosinophil differentiation [56] Fendrr expression in the murine lateral mesoderm; heart and body wall development [57] Gomafu CNS neurons; neuronal stem cell development; Schizophrenia [58] HOTAIRM1 myelopoesis; modulation of the expression of the HOXA cluster [89] Jpx X-inactivation; activation of XIST, probably through interference with Tsix [33] LincRNA-EPS repression of the erythroid differentiation and stimulation of apoptosis [90] Linc-MD1 competing endogenous lncRNA (ceRNA); control of myelopoesis, decoy for MIAT / RNCR2 retina development; Myocard infarction [117,118] Myh7-as co-repressor; NAT; regulation of the expression ratio of the sarcomeric components Myh6 and Myh7 [119] Neurological diseases BACE1-AS regulation of the mRNA stability and transcriptional co-activation of BACE1;…”

Section: Development Cellular Maintenance and Imprintingmentioning

confidence: 99%