A5050225998- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Chromosomal and Genetic Variations
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Genetic Mapping and Diversity in Plants and Animals
- RNA Research and Splicing
- Genetic diversity and population structure
- Animal Genetics and Reproduction
- Cancer-related molecular mechanisms research
- Pluripotent Stem Cells Research
- RNA and protein synthesis mechanisms
- Genetics and Neurodevelopmental Disorders
- RNA regulation and disease
- Animal Ecology and Behavior Studies
- Genomics and Phylogenetic Studies
- Cancer-related gene regulation
- Bat Biology and Ecology Studies
- Genetic Syndromes and Imprinting
- interferon and immune responses
- Molecular Biology Techniques and Applications
- thermodynamics and calorimetric analyses
- Evolution and Genetic Dynamics
- Chemical Reactions and Isotopes
University of Oxford
2016-2025
Plekhanov Russian University of Economics
2019-2021
Hammersmith Hospital
1998-2010
Medical Research Council
2001-2008
Imperial College London
2005-2008
Nara Institute of Science and Technology
2004
University of Amsterdam
2004
Institute of Cytology and Genetics
1988-2004
In-Q-Tel
2002
Russian Academy of Sciences
1998
It is generally accepted that paternally imprinted X inactivation occurs exclusively in extraembryonic lineages of mouse embryos, whereas cells the embryo proper, derived from inner cell mass (ICM), undergo only random inactivation. Here we show inactivation, fact, all early embryos and paternal then selectively reactivated allocated to ICM. This contrasts with more differentiated types where highly stable irreversible. Our observations illustrate an important component genome plasticity...
The ribonuclease III enzyme Dicer is essential for the processing of micro-RNAs (miRNAs) and small interfering RNAs (siRNAs) from double-stranded RNA precursors. miRNAs siRNAs regulate chromatin structure, gene transcription, mRNA stability, translation in a wide range organisms. To provide model system to explore role Dicer-generated differentiation mammalian cells vivo, we have generated conditional allele. Deletion at an early stage T cell development compromised survival αβ lineage...
Polycomb steps to inactivate X XX females silence one of their chromosomes. This involves a process whereby noncoding RNA known as Xist coats the chromosomes and recruits chromatin silencing factors. The complexes PRC1 PRC2 are also be involved in chromosome inactivation. Almeida et al. elucidate key role specific complex, PCGF3/5-PRC1, initiating recruitment by RNA. They further demonstrate that is critical for Xist-mediated female embryogenesis. Science , this issue p. 1081
Abstract The Polycomb repressive complexes PRC1 and PRC2 play a central role in developmental gene regulation multicellular organisms. modify chromatin by catalysing histone H2A lysine 119 ubiquitylation (H2AK119u1), H3 27 methylation (H3K27me3), respectively. Reciprocal crosstalk between these modifications is critical for the formation of stable domains at target loci. While molecular mechanism recognition H3K27me3 well defined, interaction with H2AK119u1 poorly understood. Here we...
Highlights•An shRNA screen identifies factors implicated in chromosome silencing by Xist RNA•Rbm15, Wtap, and Spen are required for Xist-mediated silencing•Rbm15 is important efficient deposition of H3K27me3 on the inactive chromosome•Rbm15, co-localize with RNA perichromatin spacesSummaryX-chromosome inactivation process that evolved mammals to equalize levels X-linked gene expression XX females relative XY males. Silencing a single X female cells mediated non-coding Xist. Although progress...
The Xist locus plays a central role in the regulation of X chromosome inactivation mammals, although its exact mode action remains to be elucidated. Evolutionary studies are important identifying conserved genomic regions and defining their possible function. Here we report cloning, sequence analysis, detailed characterization gene from four closely related species common vole (field mouse), Microtus arvalis . Our analysis reveals that there is overall conservation structure both between...
X-chromosome inactivation, which occurs in female eutherian mammals is controlled by a complex X-linked locus termed the X-inactivation center (XIC). Previously it was proposed that genes of XIC evolved, at least part, as result pseudogenization protein-coding genes. In this study we show key gene Xist, displays fragmentary homology to Lnx3, emerged de novo early eutherians integration mobile elements gave rise simple tandem repeats. The Xist promoter region and four out ten exons found...
The nuclear matrix protein Cip1-interacting zinc finger 1 (CIZ1) promotes DNA replication in association with cyclins and has been linked to adult pediatric cancers. Here we show that CIZ1 is highly enriched on the inactive X chromosome (Xi) mouse human female cells retained by interaction RNA-dependent matrix. recruited Xi response expression of inactive-specific transcript (Xist) RNA during earliest stages inactivation embryonic stem dependent C-terminal anchor domain E repeats Xist ....
Abstract Xist RNA, the master regulator of X chromosome inactivation, acts in cis to induce chromosome-wide silencing. Whilst recent studies have defined candidate silencing factors, their relative contribution repressing different genes, and relationship with one another is poorly understood. Here we describe a systematic analysis Xist-mediated allelic mouse embryonic stem cell-based models. Using machine learning approach identify distance locus prior gene expression levels as key...
The inactive X chromosome (Xi) in female mammals adopts an atypical higher-order chromatin structure, manifested as a global loss of local topologically associated domains (TADs), A/B compartments and formation two mega-domains. Here we demonstrate that the non-canonical SMC family protein, SmcHD1, which is important for gene silencing on Xi, contributes to this unique architecture. Specifically, allelic mapping transcriptome epigenome SmcHD1 mutant cells reveals appearance sub-megabase...
The Smchd1 gene encodes a large protein with homology to the SMC family of proteins involved in chromosome condensation and cohesion. Previous studies have found that has an important role CpG island (CGI) methylation on inactive X (Xi) stable silencing some Xi genes. In this study, using genome-wide expression analysis, we showed is required for around 10% genes Xi, apparently independent CGI hypomethylation, and, moreover, these nonrandomly occur clusters. Additionally, at cluster four...
Visualizing Xist RNA dynamics The noncoding Xist, which controls the process of X chromosome inactivation in mammals, accumulates and spreads over from it is transcribed. underlying basis for this unusual behavior poorly understood. Using a new imaging approach called RNA-SPLIT time-resolved analysis molecules at super-resolution, Rodermund et al. analyzed fundamental parameters normal cells after perturbation factors implicated function. authors provide insights into localization...
The propagation of X chromosome inactivation is thought to be mediated by the cis-limited spreading nonprotein coding Xist transcript. In this report we have investigated localization RNA on rodent metaphase chromosomes. We show that exhibits a banded pattern inactive and excluded from regions constitutive heterochromatin. banding suggests preferential association with gene-rich, G-light regions. Analysis X:autosome rearrangements revealed restricted into cis-linked autosomal material...
In female mammals, one of the two X chromosomes is transcriptionally silenced to equalize X-linked gene dosage relative XY males, a process termed chromosome inactivation. Mechanistically, this thought occur via directed recruitment chromatin modifying factors by master regulator, X-inactive specific transcript (Xist) RNA, which localizes in cis along entire length chromosome. A well-studied example polycomb repressive complex 2 (PRC2), for there evidence direct interaction involving PRC2...
The chromosomal protein SMCHD1 plays an important role in epigenetic silencing at diverse loci, including the inactive X chromosome, imprinted genes, and facioscapulohumeral muscular dystrophy locus. Although homology with canonical SMC family proteins suggests a chromosome organization, mechanisms underlying function target site selection remain poorly understood. Here we show that forms active GHKL-ATPase homodimer, contrasting complexes, which exist as tripartite ring structures. Electron...
We and others have recently reported that the SMC protein Smchd1 is a regulator of chromosome conformation. critical for structure inactive X at autosomal targets such as Hox genes. However, it unknown how recruited to these sites. Here, we report localizes via Xist-HnrnpK-PRC1 (polycomb repressive complex 1) pathway. Contrary previous reports, does not bind Xist or other RNA molecules with any specificity. Rather, localization H2AK119ub dependent. Following perturbation this interaction,...
<ns4:p><ns4:bold>Background</ns4:bold>: X chromosome inactivation in mammals is regulated by the non-coding (nc) RNA, Xist, which represses from it transcribed. High levels of N6-methyladenosine (m6A) RNA modification occur within Xist exon I, close to 5’ end transcript, and also further 3’, VII. The m6A catalysed METTL3/14 complex that directed specific targets, including binding protein RBM15/15B. has been reported be important for Xist–mediated gene silencing. </ns4:p><ns4:p>...