Enhanced chromatin accessibility contributes to X chromosome dosage compensation in mammals

Abstract Background Precise gene dosage of the X chromosomes is critical for normal development and cellular function. In mice, XX female somatic cells show transcriptional X chromosome upregulation of their single active X chromosome, while the other X chromosome is inactive. Moreover, the inactive...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Irene Talon, Adrian Janiszewski, Bart Theeuwes, Thomas Lefevre, Juan Song, Greet Bervoets, Lotte Vanheer, Natalie De Geest, Suresh Poovathingal, Ryan Allsop, Jean-Christophe Marine, Florian Rambow, Thierry Voet, Vincent Pasque
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	X chromosome upregulation X chromosome reactivation Chromatin accessibility Gene regulatory networks iPSC reprogramming Gene dosage compensation Biology (General) QH301-705.5 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/553698c5364b4b4abcd02d2908aac7a2
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:553698c5364b4b4abcd02d2908aac7a2
record_format	dspace
spelling	oai:doaj.org-article:553698c5364b4b4abcd02d2908aac7a22021-11-08T11:17:17ZEnhanced chromatin accessibility contributes to X chromosome dosage compensation in mammals10.1186/s13059-021-02518-51474-760Xhttps://doaj.org/article/553698c5364b4b4abcd02d2908aac7a22021-11-01T00:00:00Zhttps://doi.org/10.1186/s13059-021-02518-5https://doaj.org/toc/1474-760XAbstract Background Precise gene dosage of the X chromosomes is critical for normal development and cellular function. In mice, XX female somatic cells show transcriptional X chromosome upregulation of their single active X chromosome, while the other X chromosome is inactive. Moreover, the inactive X chromosome is reactivated during development in the inner cell mass and in germ cells through X chromosome reactivation, which can be studied in vitro by reprogramming of somatic cells to pluripotency. How chromatin processes and gene regulatory networks evolved to regulate X chromosome dosage in the somatic state and during X chromosome reactivation remains unclear. Results Using genome-wide approaches, allele-specific ATAC-seq and single-cell RNA-seq, in female embryonic fibroblasts and during reprogramming to pluripotency, we show that chromatin accessibility on the upregulated mammalian active X chromosome is increased compared to autosomes. We further show that increased accessibility on the active X chromosome is erased by reprogramming, accompanied by erasure of transcriptional X chromosome upregulation and the loss of increased transcriptional burst frequency. In addition, we characterize gene regulatory networks during reprogramming and X chromosome reactivation, revealing changes in regulatory states. Our data show that ZFP42/REX1, a pluripotency-associated gene that evolved specifically in placental mammals, targets multiple X-linked genes, suggesting an evolutionary link between ZFP42/REX1, X chromosome reactivation, and pluripotency. Conclusions Our data reveal the existence of intrinsic compensatory mechanisms that involve modulation of chromatin accessibility to counteract X-to-Autosome gene dosage imbalances caused by evolutionary or in vitro X chromosome loss and X chromosome inactivation in mammalian cells.Irene TalonAdrian JaniszewskiBart TheeuwesThomas LefevreJuan SongGreet BervoetsLotte VanheerNatalie De GeestSuresh PoovathingalRyan AllsopJean-Christophe MarineFlorian RambowThierry VoetVincent PasqueBMCarticleX chromosome upregulationX chromosome reactivationChromatin accessibilityGene regulatory networksiPSC reprogrammingGene dosage compensationBiology (General)QH301-705.5GeneticsQH426-470ENGenome Biology, Vol 22, Iss 1, Pp 1-36 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	X chromosome upregulation X chromosome reactivation Chromatin accessibility Gene regulatory networks iPSC reprogramming Gene dosage compensation Biology (General) QH301-705.5 Genetics QH426-470
spellingShingle	X chromosome upregulation X chromosome reactivation Chromatin accessibility Gene regulatory networks iPSC reprogramming Gene dosage compensation Biology (General) QH301-705.5 Genetics QH426-470 Irene Talon Adrian Janiszewski Bart Theeuwes Thomas Lefevre Juan Song Greet Bervoets Lotte Vanheer Natalie De Geest Suresh Poovathingal Ryan Allsop Jean-Christophe Marine Florian Rambow Thierry Voet Vincent Pasque Enhanced chromatin accessibility contributes to X chromosome dosage compensation in mammals
description	Abstract Background Precise gene dosage of the X chromosomes is critical for normal development and cellular function. In mice, XX female somatic cells show transcriptional X chromosome upregulation of their single active X chromosome, while the other X chromosome is inactive. Moreover, the inactive X chromosome is reactivated during development in the inner cell mass and in germ cells through X chromosome reactivation, which can be studied in vitro by reprogramming of somatic cells to pluripotency. How chromatin processes and gene regulatory networks evolved to regulate X chromosome dosage in the somatic state and during X chromosome reactivation remains unclear. Results Using genome-wide approaches, allele-specific ATAC-seq and single-cell RNA-seq, in female embryonic fibroblasts and during reprogramming to pluripotency, we show that chromatin accessibility on the upregulated mammalian active X chromosome is increased compared to autosomes. We further show that increased accessibility on the active X chromosome is erased by reprogramming, accompanied by erasure of transcriptional X chromosome upregulation and the loss of increased transcriptional burst frequency. In addition, we characterize gene regulatory networks during reprogramming and X chromosome reactivation, revealing changes in regulatory states. Our data show that ZFP42/REX1, a pluripotency-associated gene that evolved specifically in placental mammals, targets multiple X-linked genes, suggesting an evolutionary link between ZFP42/REX1, X chromosome reactivation, and pluripotency. Conclusions Our data reveal the existence of intrinsic compensatory mechanisms that involve modulation of chromatin accessibility to counteract X-to-Autosome gene dosage imbalances caused by evolutionary or in vitro X chromosome loss and X chromosome inactivation in mammalian cells.
format	article
author	Irene Talon Adrian Janiszewski Bart Theeuwes Thomas Lefevre Juan Song Greet Bervoets Lotte Vanheer Natalie De Geest Suresh Poovathingal Ryan Allsop Jean-Christophe Marine Florian Rambow Thierry Voet Vincent Pasque
author_facet	Irene Talon Adrian Janiszewski Bart Theeuwes Thomas Lefevre Juan Song Greet Bervoets Lotte Vanheer Natalie De Geest Suresh Poovathingal Ryan Allsop Jean-Christophe Marine Florian Rambow Thierry Voet Vincent Pasque
author_sort	Irene Talon
title	Enhanced chromatin accessibility contributes to X chromosome dosage compensation in mammals
title_short	Enhanced chromatin accessibility contributes to X chromosome dosage compensation in mammals
title_full	Enhanced chromatin accessibility contributes to X chromosome dosage compensation in mammals
title_fullStr	Enhanced chromatin accessibility contributes to X chromosome dosage compensation in mammals
title_full_unstemmed	Enhanced chromatin accessibility contributes to X chromosome dosage compensation in mammals
title_sort	enhanced chromatin accessibility contributes to x chromosome dosage compensation in mammals
publisher	BMC
publishDate	2021
url	https://doaj.org/article/553698c5364b4b4abcd02d2908aac7a2
work_keys_str_mv	AT irenetalon enhancedchromatinaccessibilitycontributestoxchromosomedosagecompensationinmammals AT adrianjaniszewski enhancedchromatinaccessibilitycontributestoxchromosomedosagecompensationinmammals AT barttheeuwes enhancedchromatinaccessibilitycontributestoxchromosomedosagecompensationinmammals AT thomaslefevre enhancedchromatinaccessibilitycontributestoxchromosomedosagecompensationinmammals AT juansong enhancedchromatinaccessibilitycontributestoxchromosomedosagecompensationinmammals AT greetbervoets enhancedchromatinaccessibilitycontributestoxchromosomedosagecompensationinmammals AT lottevanheer enhancedchromatinaccessibilitycontributestoxchromosomedosagecompensationinmammals AT nataliedegeest enhancedchromatinaccessibilitycontributestoxchromosomedosagecompensationinmammals AT sureshpoovathingal enhancedchromatinaccessibilitycontributestoxchromosomedosagecompensationinmammals AT ryanallsop enhancedchromatinaccessibilitycontributestoxchromosomedosagecompensationinmammals AT jeanchristophemarine enhancedchromatinaccessibilitycontributestoxchromosomedosagecompensationinmammals AT florianrambow enhancedchromatinaccessibilitycontributestoxchromosomedosagecompensationinmammals AT thierryvoet enhancedchromatinaccessibilitycontributestoxchromosomedosagecompensationinmammals AT vincentpasque enhancedchromatinaccessibilitycontributestoxchromosomedosagecompensationinmammals
_version_	1718442236736176128

Enhanced chromatin accessibility contributes to X chromosome dosage compensation in mammals

Ejemplares similares