A cross-species comparison of escape from X inactivation in Eutheria: implications for evolution of X chromosome inactivation

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dc.contributor.authorAl Nadaf, Shafagh
dc.contributor.authorDeakin, Janine
dc.contributor.authorGilbert, Clement
dc.contributor.authorRobinson, Terence J
dc.contributor.authorGraves, Jennifer
dc.contributor.authorWaters, Paul
dc.date.accessioned2015-12-10T23:12:33Z
dc.date.issued2012
dc.date.updated2016-02-24T12:09:02Z
dc.description.abstractSex chromosome dosage compensation in both eutherian and marsupial mammals is achieved by X chromosome inactivation (XCI) - transcriptional repression that silences one of the two X chromosomes in the somatic cells of females. We recently used RNA fluorescent in situ hybridization (FISH) to show, in individual nuclei, that marsupial X inactivation (in the absence of XIST) occurs on a gene-by-gene basis, and that escape from inactivation is stochastic and independent of gene location. In the absence of similar data from fibroblast cell lines of eutherian representatives, a meaningful comparison is lacking. We therefore used RNA-FISH to examine XCI in fibroblast cell lines obtained from three distantly related eutherian model species: African savannah elephant (Loxodonta africana), mouse (Mus musculus) and human (Homo sapiens). We show that, unlike the orthologous marsupial X, inactivation of the X conserved region (XCR) in eutherians generally is complete. Two-colour RNA-FISH on female human, mouse and elephant interphase nuclei showed that XCR loci have monoallelic expression in almost all nuclei. However, we found that many loci located in the evolutionarily distinct recently added region (XAR) displayed reproducible locusspecific frequencies of nuclei with either one or two active X alleles. We propose that marsupial XCI retains features of an ancient incomplete silencing mechanism that was augmented by the evolution of the XIST gene that progressively stabilized the eutherian XCR. In contrast, the recently added region of the eutherian X displays an incomplete inactivation profile similar to that observed on the evolutionarily distinct marsupial X and the independently evolved monotreme X chromosomes.
dc.identifier.issn0009-5915
dc.identifier.urihttp://hdl.handle.net/1885/64030
dc.publisherSpringer
dc.sourceChromosoma
dc.subjectKeywords: RNA; animal cell; article; cell nucleus; chromosome analysis; controlled study; elephant; Eutheria; female; fibroblast culture; fluorescence in situ hybridization; gene expression; gene expression regulation; gene locus; gene silencing; human; human cell;
dc.titleA cross-species comparison of escape from X inactivation in Eutheria: implications for evolution of X chromosome inactivation
dc.typeJournal article
local.bibliographicCitation.lastpage78
local.bibliographicCitation.startpage71
local.contributor.affiliationAl Nadaf, Shafagh, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationDeakin, Janine, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationGilbert, Clement, University of Stellenbosch
local.contributor.affiliationRobinson, Terence J, University of Stellenbosch
local.contributor.affiliationGraves, Jennifer, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationWaters, Paul, College of Medicine, Biology and Environment, ANU
local.contributor.authoremailu4025957@anu.edu.au
local.contributor.authoruidAl Nadaf, Shafagh, u4389060
local.contributor.authoruidDeakin, Janine, u4025957
local.contributor.authoruidGraves, Jennifer, u4021869
local.contributor.authoruidWaters, Paul, u4025262
local.description.embargo2037-12-31
local.description.notesImported from ARIES
local.identifier.absfor060404 - Epigenetics (incl. Genome Methylation and Epigenomics)
local.identifier.absfor060407 - Genome Structure and Regulation
local.identifier.absfor060405 - Gene Expression (incl. Microarray and other genome-wide approaches)
local.identifier.absseo970106 - Expanding Knowledge in the Biological Sciences
local.identifier.ariespublicationu9511635xPUB878
local.identifier.citationvolume121
local.identifier.doi10.1007/s00412-011-0343-8
local.identifier.scopusID2-s2.0-84859766038
local.identifier.thomsonID000299328900005
local.identifier.uidSubmittedByu9511635
local.type.statusPublished Version

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