High impact information on Tsix

• Tsix controls X-chromosome inactivation (XCI) by blocking the accumulation of Xist RNA on the future active X chromosome [1].
• Deleting Tsix on one X chromosome (X(Delta)X) skews XCI toward the mutated X chromosome in the female soma [1].
• Homozygous Tsix mutant mice reveal a sex-ratio distortion and revert to random X-inactivation [1].
• Thus, with respect to choice, mutation of Tsix yields a phenotypic abnormality in heterozygotes but not homozygotes [1].
• In contrast to effects in embryonic stem cells, deleting Tsix causes ectopic X inactivation in early male embryos and inactivation of both X chromosomes in female embryos, indicating that X chromosome counting cannot override Tsix imprinting [2].

Biological context of Tsix

• This phenotype is similar to that seen with mutations that ablate Tsix, an antisense RNA initiated 3' of Xist [3].
• We propose that allele-specific Xite action promotes Tsix asymmetry and generates X chromosome inequality [4].
• Here, we discover a cis element in the mouse X-inactivation center that regulates Tsix [4].
• Each enhancer contains DNase I-hypersensitive sites and appears to confer developmental specificity to Tsix expression [5].
• Targeted mutagenesis of Tsix leads to nonrandom X inactivation [6].

Anatomical context of Tsix

• A 65 kb deletion targeted to one of the two Xs in a female ES cell line, and including both the end of the Xist gene and the site of initiation of Tsix, resulted in the exclusive inactivation of the deleted X in differentiated ES cells [7].
• Expression of Tsix is first detected in blastocysts and is imprinted with only the maternal allele transcribed [8].

Physical interactions of Tsix

• Here, we test whether Tsix RNA destabilizes Xist RNA [9].

Regulatory relationships of Tsix

• X chromosome choice is determined by asymmetric expression of Tsix whose antisense action represses Xist [4].

Other interactions of Tsix

• These experiments revealed the intergenic transcription element Xite as an enhancer of Tsix and the repeat element DXPas34 as a component of the bipartite enhancer [5].
• Critical control sequences in the Xic include the non-coding RNAs Xist and Tsix, and long-range chromatin elements [10].

Analytical, diagnostic and therapeutic context of Tsix

• Applying RNA fluorescence in situ hybridization to parthenogenetic embryos with two maternally derived X (X(M)) chromosomes and embryos with X chromosome aneuploidy such as X(P)0 (X(P), paternally derived X chromosome), X(M)X(M)X(P) and X(M)X(M)Y, we studied the control of Xist/Tsix expression for silencing the entire X chromosome in mice [11].

References