Dataset Information

Synergy of Eed and Tsix in the repression of Xist gene and X-chromosome inactivation.

ABSTRACT: X-chromosome inactivation (XCI) depends on the noncoding Xist gene. Xist transcription is negatively regulated by its antisense partner Tsix, whose disruption results in nonrandom XCI in females. However, males can maintain Xist in a repressed state without Tsix, indicating participation of additional factor(s) in the protection of the single male X from inactivation. Here, we provide evidence that the histone methyltransferase Eed is also involved in the process. Male embryonic stem cells with Eed-null and Tsix mutations (X(Delta)Y Eed-/-) showed Xist hyperactivation upon differentiation, whereas cells with either mutation alone did not. Impaired X-linked gene expression was observed in the X(Delta)Y Eed-/- ES cells at the onset of differentiation. The Xist promoter in the X(Delta)Y Eed-/- cells showed elevated histone H3-dimethyl lysine 4 modifications and lowered CpG methylation, which are characteristics of open chromatin. Hence, we identified Eed as an additional major player in the regulation of Xist expression. The synergy of Polycomb group proteins and antisense Tsix transcription in Xist gene regulation explains why males can repress Xist without Tsix.

SUBMITTER: Shibata S

PROVIDER: S-EPMC2486422 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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Synergy of Eed and Tsix in the repression of Xist gene and X-chromosome inactivation.

Shibata Shinwa S Yokota Takashi T Wutz Anton A

The EMBO journal 20080529 13

X-chromosome inactivation (XCI) depends on the noncoding Xist gene. Xist transcription is negatively regulated by its antisense partner Tsix, whose disruption results in nonrandom XCI in females. However, males can maintain Xist in a repressed state without Tsix, indicating participation of additional factor(s) in the protection of the single male X from inactivation. Here, we provide evidence that the histone methyltransferase Eed is also involved in the process. Male embryonic stem cells with ...[more]

PMID: 18511907

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Project description:BackgroundChromosome counting is a process in which cells determine somehow their intrinsic chromosome number(s). The best-studied cellular mechanism that involves chromosome counting is 'chromosome-kissing' and X-chromosome inactivation (XCI) mechanism. It is necessary for the well-known dosage compensation between the genders in mammals to balance the number of active X-chromosomes (Xa) with regard to diploid set of autosomes. At the onset of XCI, two X-chromosomes are coming in close proximity and pair physically by a specific segment denominated X-pairing region (Xpr) that involves the SLC16A2 gene.ResultsAn Ensembl BLAST search for human and mouse SLC16A2/Slc16a2 homologues revealed, that highly similar sequences can be found at almost each chromosome in the corresponding genomes. Additionally, a BLAST search for SLC16A2/TSIX/XIST (genes responsible for XCI) reveled that "SLC16A2/TSIX/XIST like sequences" cover equally all chromosomes, too. With respect to this we provide following hypotheses.HypothesesIf a single genomic region containing the SLC16A2 gene on X-chromosome is responsible for maintaining "balanced" active copy numbers, it is possible that similar sequences or gene/s have the same function on other chromosomes (autosomes). SLC16A2 like sequences on autosomes could encompass evolutionary older, but functionally active key regions for chromosome counting in early embryogenesis. Also SLC16A2 like sequence on autosomes could be involved in inappropriate chromosomes pairing and, thereby be involved in aneuploidy formation during embryogenesis and cancer development. Also, "SLC16A2/TSIX/XIST gene like sequence combinations" covering the whole genome, could be important for the determination of X:autosome ratio in cells and chromosome counting.ConclusionsSLC16A2 and/or SLC16A2/TSIX/XIST like sequence dispersed across autosomes and X-chromosome(s) could serve as bases for a counting mechanism to determine X:autosome ratio and could potentially be a mechanism by which a cell also counts its autosomes. It could also be that such specific genomic regions have the same function for each specific autosome. As errors during the obviously existing process of chromosome counting are one if not the major origin of germline/somatic aneuploidy the here presented hypotheses should further elaborated and experimentally tested.

Dataset Information

Synergy of Eed and Tsix in the repression of Xist gene and X-chromosome inactivation.

Publications

Synergy of Eed and Tsix in the repression of Xist gene and X-chromosome inactivation.

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