Activators and repressors: A balancing act for X-inactivation

Goodrich, Leeanne; Panning, Barbara; Leung, Karen

doi:10.1016/j.semcdb.2016.05.005

Cited by 7 publications

(4 citation statements)

References 64 publications

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“…In this study, we showed that Osblr8 was enriched in the promoter and 5'-and 3'-enhancers of Oct4. A similar mechanism has been observed for a well-known lncRNA Xist, which initiates X-chromosome inactivation (XCI) in females by coating the inactive X-chromosome in cis [58][59][60][61][62]. We demonstrated that Osblr8 was essential for the maintenance of this intrachromosomal looping.…”

Section: Discussionsupporting

confidence: 71%

Osblr8 orchestrates intrachromosomal loop structure required for maintaining stem cell pluripotency

Zhu¹,

Yan²,

Du³

et al. 2020

Int. J. Biol. Sci.

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Induced pluripotent stem cells (iPSCs), derived from reprogramming of somatic cells by a cocktail of transcription factors, have the capacity for unlimited self-renewal and the ability to differentiate into all of cell types present in the body. iPSCs may have therapeutic potential in regenerative medicine, replacing injured tissues or even whole organs. In this study, we examine epigenetic factors embedded in the specific 3-dimensional intrachromosomal architecture required for the activation of endogenous pluripotency genes. Using chromatin RNA in situ reverse transcription sequencing (CRIST-seq), we identified an Oct4-Sox2 binding long noncoding RNA, referred as to Osblr8, that is present in association with pluripotency status. Osblr8 was highly expressed in iPSCs and E14 embryonic stem cells, but it was silenced in fibroblasts. By using shRNA to knock down Osblr8, we found that this lncRNA was required for the maintenance of pluripotency. Overexpression of Osblr8 activated endogenous stem cell core factor genes. Mechanistically, Osblr8 participated in the formation of an intrachromosomal looping structure that is required to activate stem cell core factors during reprogramming. In summary, we have demonstrated that lncRNA Osblr8 is a chromatin architecture modulator of pluripotency-associated master gene promoters, highlighting its critical epigenetic role in reprogramming.

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Section: Discussionsupporting

confidence: 71%

Osblr8 orchestrates intrachromosomal loop structure required for maintaining stem cell pluripotency

Zhu¹,

Yan²,

Du³

et al. 2020

Int. J. Biol. Sci.

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“…Ubuquitin ligase RNF12 has the C-terminally located RING domain and the central basic domain (BD). It is involved in X-chromosome inactivation (XCI) and in mediating ubiquitination and degradation of pluripotency marker reduced expression protein 1 (REX1) [252,253]. Mutations in RNF12 were reported in X-linked intellectual disability.…”

Section: Tgf-β Signaling Pathwaymentioning

confidence: 99%

Ubiquitin Ligases Involved in the Regulation of Wnt, TGF-β, and Notch Signaling Pathways and Their Roles in Mouse Development and Homeostasis

Baloghová

Liďák

Cermak

2019

Genes

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The Wnt, TGF-β, and Notch signaling pathways are essential for the regulation of cellular polarity, differentiation, proliferation, and migration. Differential activation and mutual crosstalk of these pathways during animal development are crucial instructive forces in the initiation of the body axis and the development of organs and tissues. Due to the ability to initiate cell proliferation, these pathways are vulnerable to somatic mutations selectively producing cells, which ultimately slip through cellular and organismal checkpoints and develop into cancer. The architecture of the Wnt, TGF-β, and Notch signaling pathways is simple. The transmembrane receptor, activated by the extracellular stimulus, induces nuclear translocation of the transcription factor, which subsequently changes the expression of target genes. Nevertheless, these pathways are regulated by a myriad of factors involved in various feedback mechanisms or crosstalk. The most prominent group of regulators is the ubiquitin–proteasome system (UPS). To open the door to UPS-based therapeutic manipulations, a thorough understanding of these regulations at a molecular level and rigorous confirmation in vivo are required. In this quest, mouse models are exceptional and, thanks to the progress in genetic engineering, also an accessible tool. Here, we reviewed the current understanding of how the UPS regulates the Wnt, TGF-β, and Notch pathways and we summarized the knowledge gained from related mouse models.

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“…The lncRNA XIST, a product of the XIST gene, is located within the 500 kb stretch of XCI DNA at Xq13, which is known as the X-inactivation center (XIC); XIST is the master regulator of X chromosome inactivation in mammals ( Furlan and Rougeulle, 2016 ; Maduro et al, 2016 ). The current model proposes that XIST induces epigenetic silencing of multiple genes by recruiting the chromatin modifier, the PRC2 complex, to the XIC ( Goodrich et al, 2016 ). With the help of the high-affinity RNA-binding protein ATRX (alpha thalassemia/mental retardation syndrome X-linked), a growing number of XIST RNAs accumulate and are tethered to the X chromosome.…”

Section: Aberrantly Expressed Lncrnas and Their Implications In Humanmentioning

confidence: 99%

An Insight into the Increasing Role of LncRNAs in the Pathogenesis of Gliomas

Yan

et al. 2017

Front. Mol. Neurosci.

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Long non-coding RNAs (LncRNAs) are essential epigenetic regulators with critical roles in tumor initiation and malignant progression. However, the roles and mechanisms of aberrantly expressed lncRNAs in the pathogenesis of gliomas are not fully understood. With the development of deep sequencing analyses, an extensive amount of functional non-coding RNAs has been discovered in glioma tissues and cell lines. Additionally, the contributions of several lncRNAs, such as Hox transcript antisense intergenic RNA, H19 and Colorectal neoplasia differentially expressed, previously reported to be involved in other pathogenesis and processes to the oncogenesis of glioblastoma are currently addressed. Thus, lncRNAs detected in tumor tissues could serve as candidate diagnostic biomarkers and therapeutic targets for gliomas. To understand the potential function of lncRNAs in gliomas, in this review, we briefly describe the profile of lncRNAs in human glioma research and therapy. Then, we discuss the individual lncRNA that has been under intensive investigation in glioma research, and the focus is its mechanism and clinical implication.

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Activators and repressors: A balancing act for X-inactivation

Cited by 7 publications

References 64 publications

Osblr8 orchestrates intrachromosomal loop structure required for maintaining stem cell pluripotency

Osblr8 orchestrates intrachromosomal loop structure required for maintaining stem cell pluripotency

Ubiquitin Ligases Involved in the Regulation of Wnt, TGF-β, and Notch Signaling Pathways and Their Roles in Mouse Development and Homeostasis

An Insight into the Increasing Role of LncRNAs in the Pathogenesis of Gliomas

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