Talk:Molecular Development - X Inactivation
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Cite this page: Hill, M.A. (2024, April 19) Embryology Molecular Development - X Inactivation. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Molecular_Development_-_X_Inactivation |
2011
Histone acetylation controls the inactive X chromosome replication dynamics
Nat Commun. 2011 Mar;2:222.
Casas-Delucchi CS, Brero A, Rahn HP, Solovei I, Wutz A, Cremer T, Leonhardt H, Cardoso MC. Source 1] Department of Biology, Technische Universität Darmstadt, Darmstadt 64287, Germany. [2] Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany. [3].
Abstract
In mammals, dosage compensation between male and female cells is achieved by inactivating one female X chromosome (Xi). Late replication of Xi was proposed to be involved in the maintenance of its silenced state. Here, we show a highly synchronous replication of the Xi within 1 to 2 h during early-mid S-phase by following DNA replication in living mammalian cells with green fluorescent protein-tagged replication proteins. The Xi was replicated before or concomitant with perinuclear or perinucleolar facultative heterochromatin and before constitutive heterochromatin. Ectopic expression of the X-inactive-specific transcript (Xist) gene from an autosome imposed the same synchronous replication pattern. We used mutations and chemical inhibition affecting different epigenetic marks as well as inducible Xist expression and we demonstrate that histone hypoacetylation has a key role in controlling Xi replication. The epigenetically controlled, highly coordinated replication of the Xi is reminiscent of embryonic genome replication in flies and frogs before genome activation and might be a common feature of transcriptionally silent chromatin.
PMID: 21364561
2010
Active Chromatin Marks Are Retained on X Chromosomes Lacking Gene or Repeat Silencing Despite XIST/Xist Expression in Somatic Cell Hybrids
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0010787
Analysis of active and inactive X chromosome architecture reveals the independent organization of 30 nm and large-scale chromatin structures
Mol Cell. 2010 Nov 12;40(3):397-409.
Naughton C, Sproul D, Hamilton C, Gilbert N. S ource Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh EH4 2XR, UK. Abstract Using a genetic model, we present a high-resolution chromatin fiber analysis of transcriptionally active (Xa) and inactive (Xi) X chromosomes packaged into euchromatin and facultative heterochromatin. Our results show that gene promoters have an open chromatin structure that is enhanced upon transcriptional activation but the Xa and the Xi have similar overall 30 nm chromatin fiber structures. Therefore, the formation of facultative heterochromatin is dependent on factors that act at a level above the 30 nm fiber and transcription does not alter bulk chromatin fiber structures. However, large-scale chromatin structures on Xa are decondensed compared with the Xi and transcription inhibition is sufficient to promote large-scale chromatin compaction. We show a link between transcription and large-scale chromatin packaging independent of the bulk 30 nm chromatin fiber and propose that transcription, not the global compaction of 30 nm chromatin fibers, determines the cytological appearance of large-scale chromatin structures.
Copyright © 2010 Elsevier Inc. All rights reserved.
PMID: 21070966
Female-biased expression of long non-coding RNAs in domains that escape X-inactivation in mouse
BMC Genomics. 2010 Nov 3;11:614.
Reinius B, Shi C, Hengshuo L, Sandhu KS, Radomska KJ, Rosen GD, Lu L, Kullander K, Williams RW, Jazin E. Source Department of Evolution and Development, EBC, Uppsala University, Sweden. bjorn.reinius@ebc.uu.se Abstract BACKGROUND: Sexual dimorphism in brain gene expression has been recognized in several animal species. However, the relevant regulatory mechanisms remain poorly understood. To investigate whether sex-biased gene expression in mammalian brain is globally regulated or locally regulated in diverse brain structures, and to study the genomic organisation of brain-expressed sex-biased genes, we performed a large scale gene expression analysis of distinct brain regions in adult male and female mice.
RESULTS: This study revealed spatial specificity in sex-biased transcription in the mouse brain, and identified 173 sex-biased genes in the striatum; 19 in the neocortex; 12 in the hippocampus and 31 in the eye. Genes located on sex chromosomes were consistently over-represented in all brain regions. Analysis on a subset of genes with sex-bias in more than one tissue revealed Y-encoded male-biased transcripts and X-encoded female-biased transcripts known to escape X-inactivation. In addition, we identified novel coding and non-coding X-linked genes with female-biased expression in multiple tissues. Interestingly, the chromosomal positions of all of the female-biased non-coding genes are in close proximity to protein-coding genes that escape X-inactivation. This defines X-chromosome domains each of which contains a coding and a non-coding female-biased gene. Lack of repressive chromatin marks in non-coding transcribed loci supports the possibility that they escape X-inactivation. Moreover, RNA-DNA combined FISH experiments confirmed the biallelic expression of one such novel domain.
CONCLUSION: This study demonstrated that the amount of genes with sex-biased expression varies between individual brain regions in mouse. The sex-biased genes identified are localized on many chromosomes. At the same time, sexually dimorphic gene expression that is common to several parts of the brain is mostly restricted to the sex chromosomes. Moreover, the study uncovered multiple female-biased non-coding genes that are non-randomly co-localized on the X-chromosome with protein-coding genes that escape X-inactivation. This raises the possibility that expression of long non-coding RNAs may play a role in modulating gene expression in domains that escape X-inactivation in mouse.
PMID: 21047393
2007
Meiotic sex chromosome inactivation
Development. 2007 May;134(10):1823-31. Epub 2007 Feb 28.
Turner JM.
Division of Stem Cell Biology and Developmental Genetics, MRC NIMR, The Ridgeway, Mill Hill, London NW7 1AA, UK. jturner@nimr.mrc.ac.uk Abstract X chromosome inactivation is most commonly studied in the context of female mammalian development, where it performs an essential role in dosage compensation. However, another form of X-inactivation takes place in the male, during spermatogenesis, as germ cells enter meiosis. This second form of X-inactivation, called meiotic sex chromosome inactivation (MSCI) has emerged as a novel paradigm for studying the epigenetic regulation of gene expression. New studies have revealed that MSCI is a special example of a more general mechanism called meiotic silencing of unsynapsed chromatin (MSUC), which silences chromosomes that fail to pair with their homologous partners and, in doing so, may protect against aneuploidy in subsequent generations. Furthermore, failure in MSCI is emerging as an important etiological factor in meiotic sterility.
PMID: 17329371 http://www.ncbi.nlm.nih.gov/pubmed/17329371
2006
The X chromosome is organized into a gene-rich outer rim and an internal core containing silenced nongenic sequences
Proc Natl Acad Sci U S A. 2006 May 16;103(20):7688-93. Epub 2006 May 8.
Clemson CM, Hall LL, Byron M, McNeil J, Lawrence JB. Department of Cell Biology, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, MA 01655, USA.
Abstract
We investigated whether genes escape X chromosome inactivation by positioning outside of the territory defined by XIST RNA. Results reveal an unanticipated higher order organization of genes and noncoding sequences. All 15 X-linked genes, regardless of activity, position on the border of the XIST RNA territory, which resides outside of the DAPI-dense Barr body. Although more strictly delineated on the inactive X chromosome (Xi), all genes localized predominantly to the outer rim of the Xi and active X chromosome. This outer rim is decorated only by X chromosome DNA paints and is excluded from both the XIST RNA and dense DAPI staining. The only DNA found well within the Barr body and XIST RNA territory was centromeric and Cot-1 DNA; hence, the core of the X chromosome essentially excludes genes and is composed primarily of noncoding repeat-rich DNA. Moreover, we show that this core of repetitive sequences is expressed throughout the nucleus yet is silenced throughout Xi, providing direct evidence for chromosome-wide regulation of "junk" DNA transcription. Collective results suggest that the Barr body, long presumed to be the physical manifestation of silenced genes, is in fact composed of a core of silenced noncoding DNA. Instead of acting at a local gene level, XIST RNA appears to interact with and silence core architectural elements to effectively condense and shut down the Xi.
PMID: 16682630 http://www.ncbi.nlm.nih.gov/pubmed/16682630
http://www.pnas.org/content/103/20/7688.full
