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A functional role for Tsix transcription in blocking Xist RNA accumulation but not in X-chromosome choice.

ABSTRACT: In female mammals, up-regulation of Xist triggers X-chromosome inactivation in cis. Up-regulation is inhibited by sequences 3' to Xist contained within the antisense locus, Tsix. Inhibition could depend on transcription of Tsix and/or on DNA elements therein. Here we test the role of Tsix transcription by augmenting the duration and strength of Tsix expression. We find that Tsix hypertranscription is sufficient to block Xist RNA accumulation in a cis-limited manner. We propose that Tsix transcription is necessary to restrict Xist activity on the future active X and, conversely, that Tsix repression is required for Xist RNA accumulation on the future inactive X. We also find that Tsix hypertranscription does not affect X-chromosome choice. Thus, choice is mediated by elements within Tsix that are independent of promoter activity.

SUBMITTER: Stavropoulos N

PROVIDER: S-EPMC56944 | biostudies-literature | 2001 Aug

REPOSITORIES: biostudies-literature

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A functional role for Tsix transcription in blocking Xist RNA accumulation but not in X-chromosome choice.

Stavropoulos N N Lu N N Lee J T JT

Proceedings of the National Academy of Sciences of the United States of America 20010731 18

In female mammals, up-regulation of Xist triggers X-chromosome inactivation in cis. Up-regulation is inhibited by sequences 3' to Xist contained within the antisense locus, Tsix. Inhibition could depend on transcription of Tsix and/or on DNA elements therein. Here we test the role of Tsix transcription by augmenting the duration and strength of Tsix expression. We find that Tsix hypertranscription is sufficient to block Xist RNA accumulation in a cis-limited manner. We propose that Tsix transcri ...[more]

PMID: 11481444

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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

A functional role for Tsix transcription in blocking Xist RNA accumulation but not in X-chromosome choice.

Publications

A functional role for Tsix transcription in blocking Xist RNA accumulation but not in X-chromosome choice.

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