TY - JOUR
T1 - XIST dampens X chromosome activity in a SPEN-dependent manner during early human development
AU - Alfeghaly, Charbel
AU - Castel, Gaël
AU - Cazottes, Emmanuel
AU - Moscatelli, Madeleine
AU - Moinard, Eva
AU - Casanova, Miguel
AU - Boni, Juliette
AU - Mahadik, Kasturi
AU - Lammers, Jenna
AU - Freour, Thomas
AU - Chauviere, Louis
AU - Piqueras, Carla
AU - Boers, Ruben
AU - Boers, Joachim
AU - Gribnau, Joost
AU - David, Laurent
AU - Ouimette, Jean François
AU - Rougeulle, Claire
N1 - Publisher Copyright: © The Author(s) 2024.
PY - 2024/10
Y1 - 2024/10
N2 - XIST (X-inactive specific transcript) long noncoding RNA (lncRNA) is responsible for X chromosome inactivation (XCI) in placental mammals, yet it accumulates on both X chromosomes in human female preimplantation embryos without triggering X chromosome silencing. The XACT (X-active coating transcript) lncRNA coaccumulates with XIST on active X chromosomes and may antagonize XIST function. Here, we used human embryonic stem cells in a naive state of pluripotency to assess the function of XIST and XACT in shaping the X chromosome chromatin and transcriptional landscapes during preimplantation development. We show that XIST triggers the deposition of polycomb-mediated repressive histone modifications and dampens the transcription of most X-linked genes in a SPEN-dependent manner, while XACT deficiency does not significantly affect XIST activity or X-linked gene expression. Our study demonstrates that XIST is functional before XCI, confirms the existence of a transient process of X chromosome dosage compensation and reveals that XCI and dampening rely on the same set of factors.
AB - XIST (X-inactive specific transcript) long noncoding RNA (lncRNA) is responsible for X chromosome inactivation (XCI) in placental mammals, yet it accumulates on both X chromosomes in human female preimplantation embryos without triggering X chromosome silencing. The XACT (X-active coating transcript) lncRNA coaccumulates with XIST on active X chromosomes and may antagonize XIST function. Here, we used human embryonic stem cells in a naive state of pluripotency to assess the function of XIST and XACT in shaping the X chromosome chromatin and transcriptional landscapes during preimplantation development. We show that XIST triggers the deposition of polycomb-mediated repressive histone modifications and dampens the transcription of most X-linked genes in a SPEN-dependent manner, while XACT deficiency does not significantly affect XIST activity or X-linked gene expression. Our study demonstrates that XIST is functional before XCI, confirms the existence of a transient process of X chromosome dosage compensation and reveals that XCI and dampening rely on the same set of factors.
UR - http://www.scopus.com/inward/record.url?scp=85195186415&partnerID=8YFLogxK
U2 - 10.1038/s41594-024-01325-3
DO - 10.1038/s41594-024-01325-3
M3 - Article
C2 - 38834912
AN - SCOPUS:85195186415
SN - 1545-9993
VL - 31
SP - 1589
EP - 1600
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 10
ER -