Your browser doesn't support javascript.
loading
XIST directly regulates X-linked and autosomal genes in naive human pluripotent cells.
Dror, Iris; Chitiashvili, Tsotne; Tan, Shawn Y X; Cano, Clara T; Sahakyan, Anna; Markaki, Yolanda; Chronis, Constantinos; Collier, Amanda J; Deng, Weixian; Liang, Guohao; Sun, Yu; Afasizheva, Anna; Miller, Jarrett; Xiao, Wen; Black, Douglas L; Ding, Fangyuan; Plath, Kathrin.
Affiliation
  • Dror I; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Chitiashvili T; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Tan SYX; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Cano CT; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Sahakyan A; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Markaki Y; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Structural and Chemical Biology & Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, UK.
  • Chronis C; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA.
  • Collier AJ; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Deng W; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Liang G; Department of Biomedical Engineering, University of California Irvine, Irvine, CA 92697, USA.
  • Sun Y; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Afasizheva A; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Miller J; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Xiao W; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Black DL; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Ding F; Department of Biomedical Engineering, University of California Irvine, Irvine, CA 92697, USA; Department of Developmental and Cell Biology, Department of Pharmaceutical Sciences, University of California Irvine, Irvine, CA 92697, USA.
  • Plath K; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: kplath@mednet.ucla.edu.
Cell ; 187(1): 110-129.e31, 2024 01 04.
Article in En | MEDLINE | ID: mdl-38181737
ABSTRACT
X chromosome inactivation (XCI) serves as a paradigm for RNA-mediated regulation of gene expression, wherein the long non-coding RNA XIST spreads across the X chromosome in cis to mediate gene silencing chromosome-wide. In female naive human pluripotent stem cells (hPSCs), XIST is in a dispersed configuration, and XCI does not occur, raising questions about XIST's function. We found that XIST spreads across the X chromosome and induces dampening of X-linked gene expression in naive hPSCs. Surprisingly, XIST also targets specific autosomal regions, where it induces repressive chromatin changes and gene expression dampening. Thereby, XIST equalizes X-linked gene dosage between male and female cells while inducing differences in autosomes. The dispersed Xist configuration and autosomal localization also occur transiently during XCI initiation in mouse PSCs. Together, our study identifies XIST as the regulator of X chromosome dampening, uncovers an evolutionarily conserved trans-acting role of XIST/Xist, and reveals a correlation between XIST/Xist dispersal and autosomal targeting.
Subject(s)
Key words
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: 1 Database: MEDLINE Main subject: X Chromosome / Genes, X-Linked / RNA, Long Noncoding Type of study: Prognostic_studies Limits: Animals / Female / Humans / Male Language: En Year: 2024 Type: Article
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: 1 Database: MEDLINE Main subject: X Chromosome / Genes, X-Linked / RNA, Long Noncoding Type of study: Prognostic_studies Limits: Animals / Female / Humans / Male Language: En Year: 2024 Type: Article