A new Xist allele driven by a constitutively active promoter is dominated by Xist locus environment and exhibits the parent-of-origin effects

  title={A new Xist allele driven by a constitutively active promoter is dominated by Xist locus environment and exhibits the parent-of-origin effects},
  author={Yuko Amakawa and Yuka Sakata and Yuko Hoki and Satoru Arata and Seiji Shioda and Tatsuo Fukagawa and Hiroyuki Sasaki and Takashi Sado},
  pages={4299 - 4308}
The dosage difference of X-linked genes between the sexes in mammals is compensated for by genetic inactivation of one of the X chromosomes in XX females. A noncoding RNA transcribed from the Xist gene at the onset of X chromosome inactivation coats the X chromosome in cis and induces chromosome-wide heterochromatinization. Here, we report a new Xist allele (XistCAG) driven by a CAG promoter, which is known to be constitutively active in many types of cells. The paternal transmission of XistCAG… 

Figures from this paper

Defects in dosage compensation impact global gene regulation in the mouse trophoblast
The genome-wide impact of Xist RNA lacking the A-repeat suggests a significant role for Xist in gene regulation beyond imprinted X inactivation, and it is likely that dosage compensation is required not only for equalizing X-linked gene expression between the sexes but also for proper global gene regulation in differentiated female somatic cells.
What makes the maternal X chromosome resistant to undergoing imprinted X inactivation?
  • T. Sado
  • Biology
    Philosophical Transactions of the Royal Society B: Biological Sciences
  • 2017
There is a prominent difference in the chromatin structure at the Xist locus depending on the parental origin, which I suggest might account for the repression of maternal Xist in the absence of maternal Tsix at the preimplantation stages.
Ectopic Splicing Disturbs the Function of Xist RNA to Establish the Stable Heterochromatin State
It is demonstrated that ectopic splicing taking place to produce XistIVS RNA disturbs its function to properly establish stable XCI state and warrants the potential of XistivS RNA to provide further insight into the understanding of how Xist RNA contributes to establish sustainable heterochromatin.
Control of Embryonic Gene Expression and Epigenetics
In the early stages of preimplantation embryo development, maternal mRNAs direct embryonic development, and a differential methylation pattern is maintained although some show stage‐specific changes.
Gender, Genoma, and Health
  • E. Bonora
  • Medicine, Political Science
    Health and Gender
  • 2019
This work has shown that the integration of sex and gender considerations into health research can strengthen the overall health evidence base, facilitate specificity in health policies and planning, guide clinicians to better tailor medical care to individuals, and contribute to reach health equity goals.


A proximal conserved repeat in the Xist gene is essential as a genomic element for X-inactivation in mouse
It is demonstrated that the DNA sequence deleted on the mutated X, most probably the A-repeat, is essential as a genomic element for the appropriate transcriptional regulation of the Xist/Tsix loci and subsequent X-inactivation in the mouse embryo.
Evidence of Xist RNA-independent initiation of mouse imprinted X-chromosome inactivation
It is found that silencing of Xp-linked genes can initiate in the absence of paternal Xist; Xist is, however, required to stabilize silencing along the Xp.
Regulation of imprinted X-chromosome inactivation in mice by Tsix.
Genetic evidence is provided that Tsix plays a crucial role in maintaining Xist silencing in cis and in regulation of imprinted X-inactivation in the extra-embryonic tissues.
Xist-deficient mice are defective in dosage compensation but not spermatogenesis.
The results indicate that the Xist RNA is required for female dosage compensation but plays no role in spermatogenesis.
The role of maternal-specific H3K9me3 modification in establishing imprinted X-chromosome inactivation and embryogenesis in mice
It is shown, using a highly reproducible chromatin immunoprecipitation method that facilitates chromatin analysis of preimplantation embryos, that H3K9me3 is enriched at the Xist promoter region, preventing Xm-Xist activation by RNF12.
Skewing X chromosome choice by modulating sense transcription across the Xist locus.
Analysis of a series of targeted mutations at the 5' end of the Xist locus indicates that X chromosome choice is determined by the balance of Xist sense and antisense transcription prior to the onset of random X inactivation.
Mosaic methylation of Xist gene before chromosome inactivation in undifferentiated female mouse embryonic stem and embryonic germ cells
  • T. Sado, T. Tada, N. Takagi
  • Biology
    Developmental dynamics : an official publication of the American Association of Anatomists
  • 1996
It is likely that the imprint responsible for the nonrandom XP inactivation in early mouse development has been erased or masked in female ES cells, and these findings are at variance with the view that Xist expression and X inactivation are controlled by preemptive methylation in undifferentiated ES cells and probably in epiblast.