X Chromosome Inactivation

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Nuclei: Function, Transport and Receptors".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 18911

Special Issue Editor


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Guest Editor
The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
Interests: X chromosome inactivation; pluripotent stem cells; epigenetic silencing

Special Issue Information

Dear Colleagues,

X chromosome inactivation (XCI) facilitates dosage compensation of X-linked gene expression between male and female mammals, by selectively silencing the majority of genes on one of the two female X chromosomes. Achieving this requires a cascade of molecular mechanisms that begins with the upregulation of a single non-coding RNA and results in a functionally repressed X chromosome that displays epigenetically remodeled chromatin, chromosome conformation, and nuclear positioning. This process is of critical importance, as failure to establish XCI is incompatible with female life and the mechanisms employed must be robust enough to allow the silent state to be mitotically heritable for the entire life of the organism.

Over more than fifty years of research, XCI has become a paradigm for gene silencing. The study of XCI has led to fundamental changes in how we understand the roles of chromatin modifications, non-coding RNA, and nuclear architecture on both the establishment and maintenance of gene repression. Moreover, processes surrounding XCI are now known to have a profound effect on the functionality of female pluripotent stem cells. With several major advances to the field recently reported, this Special Issue will review our current understanding of XCI biology and relate this to gene silencing more broadly.

Dr. Andrew Keniry
Guest Editor

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Keywords

  • X chromosome inactivation
  • epigenetics
  • gene silencing
  • non-coding RNA
  • chromatin
  • chromosome architecture

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Published Papers (3 papers)

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Research

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11 pages, 947 KiB  
Article
Large-Scale Analysis of X Inactivation Variations between Primed and Naïve Human Embryonic Stem Cells
by Roni Sarel-Gallily and Nissim Benvenisty
Cells 2022, 11(11), 1729; https://doi.org/10.3390/cells11111729 - 24 May 2022
Cited by 3 | Viewed by 2431
Abstract
X chromosome inactivation is a mammalian dosage compensation mechanism, where one of two X chromosomes is randomly inactivated in female cells. Previous studies have suggested that primed human embryonic stem cells (hESCs) maintain an eroded state of the X chromosome and do not [...] Read more.
X chromosome inactivation is a mammalian dosage compensation mechanism, where one of two X chromosomes is randomly inactivated in female cells. Previous studies have suggested that primed human embryonic stem cells (hESCs) maintain an eroded state of the X chromosome and do not express XIST, while in naïve transition, both XIST and the eroded X chromosome are reactivated. However, the pattern of chromosome X reactivation in naïve hESCs remains mainly unknown. In this study, we examine the variations in the status of X chromosome between primed and naïve hESCs by analyzing RNA sequencing samples from different studies. We show that most samples of naïve hESCs indeed reactivate XIST and there is an increase in gene expression levels on chromosome X. However, most of the naïve samples do not fully activate chromosome X in a uniform manner and present a distinct eroded pattern, probably as a result of XIST reactivation and initiation of re-inactivation of chromosome X. This large-scale analysis provides a higher-resolution description of the changes occurring in chromosome X during primed-to-naïve transition and emphasizes the importance of taking these variations into consideration when studying X inactivation in embryonic development. Full article
(This article belongs to the Special Issue X Chromosome Inactivation)
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Review

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20 pages, 1448 KiB  
Review
Mechanisms of Choice in X-Chromosome Inactivation
by Giulia Furlan and Rafael Galupa
Cells 2022, 11(3), 535; https://doi.org/10.3390/cells11030535 - 3 Feb 2022
Cited by 22 | Viewed by 7600 | Correction
Abstract
Early in development, placental and marsupial mammals harbouring at least two X chromosomes per nucleus are faced with a choice that affects the rest of their lives: which of those X chromosomes to transcriptionally inactivate. This choice underlies phenotypical diversity in the composition [...] Read more.
Early in development, placental and marsupial mammals harbouring at least two X chromosomes per nucleus are faced with a choice that affects the rest of their lives: which of those X chromosomes to transcriptionally inactivate. This choice underlies phenotypical diversity in the composition of tissues and organs and in their response to the environment, and can determine whether an individual will be healthy or affected by an X-linked disease. Here, we review our current understanding of the process of choice during X-chromosome inactivation and its implications, focusing on the strategies evolved by different mammalian lineages and on the known and unknown molecular mechanisms and players involved. Full article
(This article belongs to the Special Issue X Chromosome Inactivation)
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25 pages, 15254 KiB  
Review
New Insights into X-Chromosome Reactivation during Reprogramming to Pluripotency
by Amitesh Panda, Jan J. Zylicz and Vincent Pasque
Cells 2020, 9(12), 2706; https://doi.org/10.3390/cells9122706 - 17 Dec 2020
Cited by 13 | Viewed by 7690
Abstract
Dosage compensation between the sexes results in one X chromosome being inactivated during female mammalian development. Chromosome-wide transcriptional silencing from the inactive X chromosome (Xi) in mammalian cells is erased in a process termed X-chromosome reactivation (XCR), which has emerged as a paradigm [...] Read more.
Dosage compensation between the sexes results in one X chromosome being inactivated during female mammalian development. Chromosome-wide transcriptional silencing from the inactive X chromosome (Xi) in mammalian cells is erased in a process termed X-chromosome reactivation (XCR), which has emerged as a paradigm for studying the reversal of chromatin silencing. XCR is linked with germline development and induction of naive pluripotency in the epiblast, and also takes place upon reprogramming somatic cells to induced pluripotency. XCR depends on silencing of the long non-coding RNA (lncRNA) X inactive specific transcript (Xist) and is linked with the erasure of chromatin silencing. Over the past years, the advent of transcriptomics and epigenomics has provided new insights into the transcriptional and chromatin dynamics with which XCR takes place. However, multiple questions remain unanswered about how chromatin and transcription related processes enable XCR. Here, we review recent work on establishing the transcriptional and chromatin kinetics of XCR, as well as discuss a model by which transcription factors mediate XCR not only via Xist repression, but also by direct targeting of X-linked genes. Full article
(This article belongs to the Special Issue X Chromosome Inactivation)
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