Cellular Resolution Maps of X Chromosome Inactivation: Implications for Neural Development, Function, and Disease

Wu, Hao; Luo, Junjie; Yu, Haibin; Rattner, Amir; Mo, Alisa; Wang, Yanshu; Smallwood, Philip M.; Erlanger, Bracha; Wheelan, Sarah J.; Nathans, Jeremy

doi:10.1016/j.neuron.2013.10.051

Cited by 179 publications

(194 citation statements)

References 51 publications

(60 reference statements)

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“…The X-chromosomal location of Ndp provides an opportunity to examine variation in Norrin action in Ndp +/-females due to variation in the topography of X chromosome inactivation (XCI). In female mouse retinas, contiguous territories that express one or the other X chromosome generally vary from tens to hundreds of microns in diameter (32,33). In earlier work with Ndp +/-females, in which the topography of the XCI mosaic was visualized with a constitu-jci.org Volume 124 Number 9 September 2014…”

Section: Claudin5mentioning

confidence: 99%

Canonical WNT signaling components in vascular development and barrier formation

Zhou¹,

Wang²,

Tischfield³

et al. 2014

J. Clin. Invest.

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267

327

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Section: Claudin5mentioning

confidence: 99%

Canonical WNT signaling components in vascular development and barrier formation

Zhou¹,

Wang²,

Tischfield³

et al. 2014

J. Clin. Invest.

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267

327

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“…8 Clinical consequences of duplications in females can vary depending upon the degree of skewing of X-inactivation, as well as variations in cell-specific patterns of gene regulation. 15 In addition, there are some genes on the X-chromosome that escape X-inactivation further complicating the assessment of dosage sensitivity. Despite these complexities, increased dosage of X-chromosome genes has been implicated in ID and autism.…”

Section: Introductionmentioning

confidence: 99%

Xp11.2 microduplications including IQSEC2, TSPYL2 and KDM5C genes in patients with neurodevelopmental disorders

et al. 2015

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Copy number variations are a common cause of intellectual disability (ID). Determining the contribution of copy number variants (CNVs), particularly gains, to disease remains challenging. Here, we report four males with ID with sub-microscopic duplications at Xp11.2 and review the few cases with overlapping duplications reported to date. We established the extent of the duplicated regions in each case encompassing a minimum of three known disease genes TSPYL2, KDM5C and IQSEC2 with one case also duplicating the known disease gene HUWE1. Patients with a duplication encompassing TSPYL2, KDM5C and IQSEC2 without gains of nearby SMC1A and HUWE1 genes have not been reported thus far. All cases presented with ID and significant deficits of speech development. Some patients also manifested behavioral disturbances such as hyperactivity and attention-deficit/ hyperactivity disorder. Lymphoblastic cell lines from patients show markedly elevated levels of TSPYL2, KDM5C and SMC1A, transcripts consistent with the extent of their CNVs. The duplicated region in our patients contains several genes known to escape X-inactivation, including KDM5C, IQSEC2 and SMC1A. In silico analysis of expression data in selected gene expression omnibus series indicates that dosage of these genes, especially IQSEC2, is similar in males and females despite the fact they escape from X-inactivation in females. Taken together, the data suggest that gains in Xp11.22 including IQSEC2 cause ID and are associated with hyperactivity and attention-deficit/hyperactivity disorder, and are likely to be dosage-sensitive in males.

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“…More recently, studies employing X--linked fluorescent reporter genes in mice also came to the conclusion that XCI is completed in the postimplantation epiblast (Fig. 2B) at the latest between E6.5 and E7.5 [31,67]. This provides further evidence that XCI is an early differentiation event during the exit from naïve pluripotency.…”

Section: Random XCI -A Hallmark Of Cell Differentiationmentioning

confidence: 69%

Developmental regulation of X-chromosome inactivation

Payer

2016

Seminars in Cell & Developmental Biology

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With the emergence of sex--determination by sex chromosomes, which differ in composition and number between males and females, appeared the need to equalize X--chromosomal gene dosage between the sexes. Mammals have devised the strategy of X--chromosome inactivation (XCI), in which one of the two X--chromosomes is rendered transcriptionally silent in females. In the mouse, the best--studied model organism with respect to XCI, this inactivation process occurs in different forms, imprinted and random, interspersed by periods of X--chromosome reactivation (XCR), which is needed to switch between the different modes of XCI. In this review, I describe the recent advances with respect to the developmental control of XCI and XCR and in particular their link to differentiation and pluripotency. Furthermore, I review the mechanisms, which influence the timing and choice, with which one of the two X--chromosomes is chosen for inactivation during random XCI. This has an impact on how females are mosaics with regard to which X--chromosome is active in different cells, which has implications on the severity of diseases caused by X--linked mutations.

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Cellular Resolution Maps of X Chromosome Inactivation: Implications for Neural Development, Function, and Disease

Cited by 179 publications

References 51 publications

Canonical WNT signaling components in vascular development and barrier formation

Canonical WNT signaling components in vascular development and barrier formation

Xp11.2 microduplications including IQSEC2, TSPYL2 and KDM5C genes in patients with neurodevelopmental disorders

Developmental regulation of X-chromosome inactivation

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