A novel X gene with a widely transcribed Y-linked homologue escapes X-inactivation in mouse and human

Agulnik, Alexander I.; Mitchell, Michael J.; Mattei, Marie-Genevı̀eve; Borsani, Giuseppe; Avner, Philip; Lerner, Jody L.; Bishop, Colin E.

doi:10.1093/hmg/3.6.879

Cited by 152 publications

(82 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a positive control, we measured expression of Smcx (Kdm5c -Mouse Genome Informatics), a gene known to escape imprinted XCI (Agulnik et al, 1994;Plusa et al, 2008). As expected, Smcx exhibited 97% biallelic expression in cells of early ICMs, demonstrating that our assay is capable of detecting biallelic X-linked gene transcription (see Fig.…”

Section: Research Articlementioning

confidence: 54%

Transcription precedes loss of Xist coating and depletion of H3K27me3 during X-chromosome reprogramming in the mouse inner cell mass

et al. 2011

View full text Add to dashboard Cite

SUMMARYRepression of Xist RNA expression is considered a prerequisite to reversal of X-chromosome inactivation (XCI) in the mouse inner cell mass (ICM), and reactivation of X-linked genes is thought to follow loss of Xist RNA coating and heterochromatic markers of inactivation, such as methylation of histone H3. We analyzed X-chromosome activity in developing ICMs and show that reactivation of gene expression from the inactive-X initiates in the presence of Xist coating and H3K27me3. Furthermore, depletion of Xist RNA coating through forced upregulation of NANOG does not result in altered reactivation kinetics. Taken together, our observations suggest that in the ICM, X-linked gene transcription and Xist coating are uncoupled. These data fundamentally alter our perception of the reactivation process and support the existence of a mechanism to reactivate Xp-linked genes in the ICM that operates independently of loss of Xist RNA and H3K27me3 from the imprinted inactive-X.

show abstract

Section: Research Articlementioning

confidence: 54%

Transcription precedes loss of Xist coating and depletion of H3K27me3 during X-chromosome reprogramming in the mouse inner cell mass

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Human and Mouse SMCX/Smcx SMCX (NM_004187) and Smcx (NM_013668) are ubiquitously expressed and escape inactivation in human and mouse (Table 1; Agulnik et al 1994b;Wu et al 1994). The Y homolog, SMCY, is also widely expressed and is conserved on the Y-chromosome in a broad range of species (Agulnik et al 1994a,b;Kent-First et al 1996).…”

Section: Characterization Of Previously Published Genesmentioning

confidence: 99%

“…The three somatic cell hybrids containing an inactive Xchromosome (X8.6T2H1, 8121-TGRD, and THX88) and an active X hybrid (Y162.HC) that were used in this study have been described elsewhere (Ledbetter et al 1991;Ellison et al 1993;Hansen et al 1996). These hybrid cell lines have been extensively used to determine the activity of X-linked genes (Agulnik et al 1994b;Hornstra and Yang 1994;Hansen et al 1996;Esposito et al 1997). We performed RT-PCR of Chinese hamster (CHO) RNA for each expressed sequence as a control for human-specific amplification.…”

Section: X-inactivation Assaysmentioning

confidence: 99%

Comparative Sequence and X-Inactivation Analyses of a Domain of Escape in Human Xp11.2 and the Conserved Segment in Mouse

Tsuchiya¹,

Greally²,

Yi³

et al. 2004

Genome Res.

View full text Add to dashboard Cite

We have performed X-inactivation and sequence analyses on 350 kb of sequence from human Xp11.2, a region shown previously to contain a cluster of genes that escape X inactivation, and we compared this region with the region of conserved synteny in mouse. We identified several new transcripts from this region in human and in mouse, which defined the full extent of the domain escaping X inactivation in both species. In human, escape from X inactivation involves an uninterrupted 235-kb domain of multiple genes. Despite highly conserved gene content and order between the two species, Smcx is the only mouse gene from the conserved segment that escapes inactivation. As repetitive sequences are believed to facilitate spreading of X inactivation along the chromosome, we compared the repetitive sequence composition of this region between the two species. We found that long terminal repeats (LTRs) were decreased in the human domain of escape, but not in the majority of the conserved mouse region adjacent to Smcx in which genes were subject to X inactivation, suggesting that these repeats might be excluded from escape domains to prevent spreading of silencing. Our findings indicate that genomic context, as well as gene-specific regulatory elements, interact to determine expression of a gene from the inactive X-chromosome.[Supplemental material is available online at www.genome.org. The sequence data from this study have been submitted to GenBank under accession no. AY451401. The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: G. Filippova and M. Delbridge.]X inactivation is a unique form of gene regulation resulting in the transcriptional silencing of most genes on one X-chromosome in each somatic cell of mammalian females. Despite the chromosome-wide nature of this phenomenon, 10% to 20% of genes on the human X-chromosome have been found to escape inactivation . Many epigenetic and functional features have been identified that distinguish genes subject to inactivation from those that escape inactivation, such as differences in replication timing, CpG island methylation, and histone modifications (for review, see Disteche et al. 2002;Brown and Greally 2003), yet the mechanisms that underlie the phenomenon of escape remain poorly understood. X inactivation is initiated by the XIST gene, followed by spreading of silencing along the X-chromosome, and maintenance of the inactive state with its associated epigenetic changes (Plath et al. 2002). Escape from inactivation could be caused by a lack of initial silencing at the onset of inactivation that occurs early in development. Alternatively, genes that escape may be initially silenced, but may fail to maintain the inactive state. Our studies that have followed expression of Smcx through the course of mouse development indicate that escape appears to be caused by failure to maintain the inactive state (Lingenfelter et al. 1998).The factors that are responsible for escape from X inactivation may reside at the level of...

show abstract

“…By determining the X-inactivation status of mouse genes, it should be possible to exclude genes that escape X inactivation in both species as candidates for the more severe Turner phenotypes, these being presumably caused by genes that escape X inactivation only in human. To date, only four mouse escape genes (Eif2s3x, Kdm5c, Kdm6a, Mid1) have been reported (Agulnik et al 1994;Dal Zotto et al 1998;Ehrmann et al 1998;Greenfield et al 1998). In addition, XIST/Xist (X-inactivation-specific transcript), a noncoding RNA essential for the onset of X inactivation, is exclusively expressed from the inactive X (Borsani et al 1991;Brockdorff et al 1991;Brown et al 1991).…”

mentioning

confidence: 99%

Global survey of escape from X inactivation by RNA-sequencing in mouse

Yang¹,

Babak²,

Shendure³

et al. 2010

Genome Res.

320

400

View full text Add to dashboard Cite

X inactivation equalizes the dosage of gene expression between the sexes, but some genes escape silencing and are thus expressed from both alleles in females. To survey X inactivation and escape in mouse, we performed RNA sequencing in Mus musculus × Mus spretus cells with complete skewing of X inactivation, relying on expression of single nucleotide polymorphisms to discriminate allelic origin. Thirteen of 393 (3.3%) mouse genes had significant expression from the inactive X, including eight novel escape genes. We estimate that mice have significantly fewer escape genes compared with humans. Furthermore, escape genes did not cluster in mouse, unlike the large escape domains in human, suggesting that expression is controlled at the level of individual genes. Our findings are consistent with the striking differences in phenotypes between female mice and women with a single X chromosome—a near normal phenotype in mice versus Turner syndrome and multiple abnormalities in humans. We found that escape genes are marked by the absence of trimethylation at lysine 27 of histone H3, a chromatin modification associated with genes subject to X inactivation. Furthermore, this epigenetic mark is developmentally regulated for some mouse genes.

show abstract

A novel X gene with a widely transcribed Y-linked homologue escapes X-inactivation in mouse and human

Cited by 152 publications

References 0 publications

Transcription precedes loss of Xist coating and depletion of H3K27me3 during X-chromosome reprogramming in the mouse inner cell mass

Transcription precedes loss of Xist coating and depletion of H3K27me3 during X-chromosome reprogramming in the mouse inner cell mass

Comparative Sequence and X-Inactivation Analyses of a Domain of Escape in Human Xp11.2 and the Conserved Segment in Mouse

Global survey of escape from X inactivation by RNA-sequencing in mouse

Contact Info

Product

Resources

About