A prominent and conserved role for YY1 in Xist transcriptional activation

Makhlouf, Mélanie; Ouimette, Jean-François; Oldfield, Andrew; Navarro, Pablo; Neuillet, Damien; Rougeulle, Claire

doi:10.1038/ncomms5878

Cited by 114 publications

(163 citation statements)

References 60 publications

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“…The nuclear scaffold protein SAF-A/hnRNPU is enriched on the Xi and is required for localizing Xist RNA to the Xi in embryonic stem cells during the initiation of XCI (48,49). The transcription factor YY1 also tethers Xist RNA to the X during the initiation and maintenance stages of XCI, and activates Xist/XIST transcription (50,51). Importantly, knockdown of hnRNPU or YY1 disrupts Xist RNA localization in post-XCI fibroblasts, resulting in a scattered pinpoint pattern similar to types II and III in lymphocytes.…”

Section: Female Lymphocytes Exhibit Partial X-reactivation Resulting Inmentioning

confidence: 99%

Unusual maintenance of X chromosome inactivation predisposes female lymphocytes for increased expression from the inactive X

Wang

Syrett

Kramer

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

244

298

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Females have a greater immunological advantage than men, yet they are more prone to autoimmune disorders. The basis for this sex bias lies in the X chromosome, which contains many immunityrelated genes. Female mammals use X chromosome inactivation (XCI) to generate a transcriptionally silent inactive X chromosome (Xi) enriched with heterochromatic modifications and XIST/Xist RNA, which equalizes gene expression between the sexes. Here, we examine the maintenance of XCI in lymphocytes from females in mice and humans. Strikingly, we find that mature naïve T and B cells have dispersed patterns of XIST/Xist RNA, and they lack the typical heterochromatic modifications of the Xi. In vitro activation of lymphocytes triggers the return of XIST/Xist RNA transcripts and some chromatin marks (H3K27me3, ubiquitin-H2A) to the Xi. Single-cell RNA FISH analysis of female T cells revealed that the X-linked immunity genes CD40LG and CXCR3 are biallelically expressed in some cells. Using knockout and knockdown approaches, we find that Xist RNA-binding proteins, YY1 and hnRNPU, are critical for recruitment of XIST/Xist RNA back to the Xi. Furthermore, we examined B cells from patients with systemic lupus erythematosus, an autoimmune disorder with a strong female bias, and observed different XIST RNA localization patterns, evidence of biallelic expression of immunity-related genes, and increased transcription of these genes. We propose that the Xi in female lymphocytes is predisposed to become partially reactivated and to overexpress immunity-related genes, providing the first mechanistic evidence to our knowledge for the enhanced immunity of females and their increased susceptibility for autoimmunity.X chromosome inactivation | XIST RNA | epigenetics | female-biased autoimmunity

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Section: Female Lymphocytes Exhibit Partial X-reactivation Resulting Inmentioning

confidence: 99%

Unusual maintenance of X chromosome inactivation predisposes female lymphocytes for increased expression from the inactive X

Wang

Syrett

Kramer

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

244

298

View full text Add to dashboard Cite

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“…While located outside of the Xic, the adaptor protein Yin Yang 1 (YY1) is a known DNA binding transcription factor which is thought to be important in up-regulating Xist expression by 6 activating the Xist promoter (Makhlouf et al 2014). It is also critical for tethering the Xist RNA to its own locus via interaction with three YY1 binding sites located near the F repeat on the genomic sequence and the transcript's C repeat sequence (Jeon and Lee 2011;Thorvaldsen et al 2011) (see Figure 1).…”

Section: 2: Regulation Of Xist/xist By Factors Outside Of Xicmentioning

confidence: 98%

The making of a Barr body: the mosaic of factors that eXIST on the mammalian inactive X chromosome

Dixon-McDougall

Brown

2016

Biochem. Cell Biol.

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During X-chromosome inactivation (XCI), nearly an entire X chromosome is permanently silenced and converted into a Barr body, providing dosage compensation for eutherians between the sexes. XCI is facilitated by the upregulation of the long non-coding RNA gene, XIST, which coats its chromosome of origin, recruits heterochromatin factors, and silences gene expression. During XCI, at least two distinct types of heterochromatin are established, and in this review we discuss the enrichment of facultative heterochromatin marks such as H3K27me3, H2AK119ub, and macroH2A as well as pericentric heterochromatin marks such as HP1, H3K9me3, and H4K20me3. The extremely stable maintenance of silencing is a product of reinforcing interactions within and between these domains. This paper "Xplores" the current knowledge of the pathways involved in XCI, how the pathways interact, and the gaps in our understanding that need to be filled.

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“…Silencing activity maps in large part to the A repeat, a short tandemly repeated region located at the 5 ′ end of Xist. In contrast, localization maps to several redundantly acting elements, including the tandem repeat regions C, E, and F (Wutz et al 2002;Jeon and Lee 2011;Makhlouf et al 2014;Yamada et al 2015).…”

mentioning

confidence: 99%

“…Accordingly, the NM proteins scaffold attachment factor A (SAF-A; hnRNPU) and hnRNP UL1 are involved in anchoring Xist RNA within Xi (Helbig and Fackelmayer 2003;Hasegawa et al 2010;Sakaguchi et al 2016). Additionally, NM protein 1 (NMP1; YY1) (Guo et al 1995) has been implicated in tethering Xist RNA to chromatin (Jeon and Lee 2011;Makhlouf et al 2014). In naïve B and T cells, Xist RNA is dispersed in the nucleoplasm but is recruited to Xi upon lymphocyte activation in a process that involves YY1 and SAF-A (Wang et al 2016).…”

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confidence: 99%

The nuclear matrix protein CIZ1 facilitates localization of Xist RNA to the inactive X-chromosome territory

et al. 2017

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The nuclear matrix protein Cip1-interacting zinc finger protein 1 (CIZ1) promotes DNA replication in association with cyclins and has been linked to adult and pediatric cancers. Here we show that CIZ1 is highly enriched on the inactive X chromosome (Xi) in mouse and human female cells and is retained by interaction with the RNA-dependent nuclear matrix. CIZ1 is recruited to Xi in response to expression of X inactive-specific transcript (Xist) RNA during the earliest stages of X inactivation in embryonic stem cells and is dependent on the C-terminal nuclear matrix anchor domain of CIZ1 and the E repeats of Xist. CIZ1-null mice, although viable, display fully penetrant female-specific lymphoproliferative disorder. Interestingly, in mouse embryonic fibroblast cells derived from CIZ1-null embryos, Xist RNA localization is disrupted, being highly dispersed through the nucleoplasm rather than focal. Focal localization is reinstated following re-expression of CIZ1. Focal localization of Xist RNA is also disrupted in activated B and T cells isolated from CIZ1-null animals, suggesting a possible explanation for female-specific lymphoproliferative disorder. Together, these findings suggest that CIZ1 has an essential role in anchoring Xist to the nuclear matrix in specific somatic lineages.

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A prominent and conserved role for YY1 in Xist transcriptional activation

Cited by 114 publications

References 60 publications

Unusual maintenance of X chromosome inactivation predisposes female lymphocytes for increased expression from the inactive X

Unusual maintenance of X chromosome inactivation predisposes female lymphocytes for increased expression from the inactive X

The making of a Barr body: the mosaic of factors that eXIST on the mammalian inactive X chromosome

The nuclear matrix protein CIZ1 facilitates localization of Xist RNA to the inactive X-chromosome territory

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