Chd8 regulates X chromosome inactivation in mouse through fine-tuning control of Xist expression. 2021

Andrea Cerase, and Alexander N Young, and Nerea Blanes Ruiz, and Andreas Buness, and Gabrielle M Sant, and Mirjam Arnold, and Monica Di Giacomo, and Michela Ascolani, and Manish Kumar, and Andreas Hierholzer, and Giuseppe Trigiante, and Sarah J Marzi, and Philip Avner
EMBL-Rome, Epigenetics and Neurobiology Unit, Monterotondo, Italy. a.cerase@qmul.ac.uk.

Female mammals achieve dosage compensation by inactivating one of their two X chromosomes during development, a process entirely dependent on Xist, an X-linked long non-coding RNA (lncRNA). At the onset of X chromosome inactivation (XCI), Xist is up-regulated and spreads along the future inactive X chromosome. Contextually, it recruits repressive histone and DNA modifiers that transcriptionally silence the X chromosome. Xist regulation is tightly coupled to differentiation and its expression is under the control of both pluripotency and epigenetic factors. Recent evidence has suggested that chromatin remodelers accumulate at the X Inactivation Center (XIC) and here we demonstrate a new role for Chd8 in Xist regulation in differentiating ES cells, linked to its control and prevention of spurious transcription factor interactions occurring within Xist regulatory regions. Our findings have a broader relevance, in the context of complex, developmentally-regulated gene expression.

UI MeSH Term Description Entries
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D004303 Dosage Compensation, Genetic Genetic mechanisms that allow GENES to be expressed at a similar level irrespective of their GENE DOSAGE. This term is usually used in discussing genes that lie on the SEX CHROMOSOMES. Because the sex chromosomes are only partially homologous, there is a different copy number, i.e., dosage, of these genes in males vs. females. In DROSOPHILA, dosage compensation is accomplished by hypertranscription of genes located on the X CHROMOSOME. In mammals, dosage compensation of X chromosome genes is accomplished by random X CHROMOSOME INACTIVATION of one of the two X chromosomes in the female. Dosage Compensation (Genetics),Gene Dosage Compensation,Hypertranscription, X-Chromosome,X-Chromosome Hypertranscription,Compensation, Dosage (Genetics),Compensation, Gene Dosage,Compensation, Genetic Dosage,Dosage Compensation, Gene,Gene Dosage Compensations,Genetic Dosage Compensation,Genetic Dosage Compensations,Hypertranscription, X Chromosome,X Chromosome Hypertranscription
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014960 X Chromosome The female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in human and other male-heterogametic species. Chromosome, X,Chromosomes, X,X Chromosomes
D049951 X Chromosome Inactivation A dosage compensation process occurring at an early embryonic stage in mammalian development whereby, at random, one X CHROMOSOME of the pair is repressed in the somatic cells of females. X Inactivation,Lyon Hypothesis,Lyonization,X-Inactivation,Chromosome Inactivation, X,Hypothesis, Lyon,Inactivation, X,Inactivation, X Chromosome,X Inactivations
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D062085 RNA, Long Noncoding A class of untranslated RNA molecules that are typically greater than 200 nucleotides in length and do not code for proteins. Members of this class have been found to play roles in transcriptional regulation, post-transcriptional processing, CHROMATIN REMODELING, and in the epigenetic control of chromatin. LincRNA,RNA, Long Untranslated,LINC RNA,LincRNAs,Long Intergenic Non-Protein Coding RNA,Long Non-Coding RNA,Long Non-Protein-Coding RNA,Long Noncoding RNA,Long ncRNA,Long ncRNAs,RNA, Long Non-Translated,lncRNA,Long Intergenic Non Protein Coding RNA,Long Non Coding RNA,Long Non Protein Coding RNA,Long Non-Translated RNA,Long Untranslated RNA,Non-Coding RNA, Long,Non-Protein-Coding RNA, Long,Non-Translated RNA, Long,Noncoding RNA, Long,RNA, Long Non Translated,RNA, Long Non-Coding,RNA, Long Non-Protein-Coding,Untranslated RNA, Long,ncRNA, Long,ncRNAs, Long

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