The large non-coding RNA Xist is the master regulator of X inactivation. Xist is negatively regulated by its antisense transcript Tsix. This repressive antisense transcription across Xist operates at least in part through the modification of the chromatin environment of the locus. However Tsix is not sufficient to repress Xist in pluripotent cells and there is emerging evidence that transcription factors associated with pluripotency are involved in Tsix-independent repression. This review focuses on recent advances in this area and discusses the implications for our understanding of Xist gene regulation at the onset of X inactivation.
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http://dx.doi.org/10.1016/j.gde.2009.03.003 | DOI Listing |
Dev Cell
January 2025
King's College London, Centre for Gene Therapy and Regenerative Medicine, School of Basic & Medical Biosciences, Faculty of Life Sciences and Medicine, London, UK; King's College London, Guy's Hospital Assisted Conception Unit, Department of Women and Children's Health, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, London, UK. Electronic address:
Female primordial germ cells (PGCs) undergo X chromosome reactivation (XCR) during genome-wide reprogramming. XCR kinetics and dynamics are poorly understood at a molecular level. Here, we apply single-cell RNA sequencing and chromatin profiling on germ cells from F mouse embryos, performing a precise appraisal of XCR spanning from migratory-stage PGCs to gonadal germ cells.
View Article and Find Full Text PDFImmunol Cell Biol
January 2025
The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
In this Research Highlight, we discuss recent research which shows that TCR-mediated activation and NF-κB signalling play an indispensable role in localising Xist RNA and its interactors to the inactive X chromosome (Xi) in T cells (left and middle). Inhibition of NF-κB disrupts this process, impairing the recruitment of silencing factors and jeopardizing the maintenance of X chromosome inactivation (right).
View Article and Find Full Text PDFBiol Sex Differ
January 2025
Department of Laboratory Medicine and Pathology, School of Medicine, University of Washington, Seattle, WA, 98195, USA.
Background: X chromosome inactivation (XCI) is a female-specific process in which one X chromosome is silenced to balance X-linked gene expression between the sexes. XCI is initiated in early development by upregulation of the lncRNA Xist on the future inactive X (Xi). A subset of X-linked genes escape silencing and thus have higher expression in females, suggesting female-specific functions.
View Article and Find Full Text PDFBMC Cancer
December 2024
Department of Pathology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Background: Male breast cancer (MBC) is a rare malignancy, but its global incidence has shown a notable increase in recent decades. Factors such as limited health literacy, inadequate health education, and reluctance to seek medical attention contribute to the late-stage diagnosis of most MBC patients. Consequently, there is an urgent need for a highly specific and sensitive diagnostic approach to MBC.
View Article and Find Full Text PDFJ Exp Med
March 2025
HSS Research Institute and David Z. Rosensweig Genomics Research Center, Inflammation and Autoimmunity Program, Hospital for Special Surgery, New York, NY, USA.
Systemic sclerosis (SSc) is an autoimmune disease that has a strong female predominance. Both the X-linked TLR7 and TLR8 can induce type I IFN (IFN-I) by plasmacytoid DCs (pDCs), which can promote fibrosis. We identified five subclusters of pDCs, including ISGhigh clusters that were over-represented in SSc patients.
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