RESUMO
A physical map encompassing approximately 2.0 megabases (Mb) in the region of the mouse X-inactivation center has been constructed. The map extends from the Gjb-1 locus to the Xist locus and demonstrates the order of probes inseparable by genetic analysis. The deduced locus order is as follows: Gjb-1, Ccg-1, DXCrc171, Rps4, Phka, DXCrc177, DXCrc318, Xist. Detailed physical mapping in the region between the Phka and Xist loci indicates the position of CpG-rich islands associated with the 5' end of genes. The DXCrc177 and DXCrc318 loci, both defined by probes derived from linking clones, are associated with CpG-rich islands. The map provides a framework for the isolation of underlying sequences in the mouse X-inactivation center region.
Assuntos
Mecanismo Genético de Compensação de Dose , Cromossomo X , Animais , Sequência de Bases , DNA de Cadeia Simples , Ligação Genética , Camundongos , Dados de Sequência Molecular , Mapeamento por RestriçãoRESUMO
The Xist gene maps to the X inactivation center region in both mouse and human, and previous analysis of the 3' end of the gene has demonstrated inactive X-specific expression, suggesting a possible role in X inactivation. We have now analyzed the entire mouse Xist gene. The mature inactive X-specific transcript is 15 kb in length and contains no conserved ORF. The Xist sequence contains a number of regions comprised of tandem repeats. Comparison with the human XIST gene demonstrates significant conservation of sequence and gene structure. Xist RNA is not associated with the translational machinery of the cell and is located almost exclusively in the nucleus. Together with conservation of inactive X-specific expression, these findings support a role for Xist in X inactivation, possibly as a functional RNA or as a chromatin organizer region.
Assuntos
Núcleo Celular/metabolismo , Mecanismo Genético de Compensação de Dose , RNA não Traduzido , Fatores de Transcrição/genética , Cromossomo X/metabolismo , Animais , Sequência de Bases , Biblioteca Gênica , Camundongos/genética , Modelos Biológicos , Dados de Sequência Molecular , RNA Longo não Codificante , RNA Mensageiro/análise , Sequências Repetitivas de Ácido Nucleico , Alinhamento de Sequência , Fatores de Transcrição/químicaRESUMO
X-chromosome inactivation in mammals is a regulatory phenomenon whereby one of the two X chromosomes in female cells is genetically inactivated, resulting in dosage compensation for X-linked genes between males and females. In both man and mouse, X-chromosome inactivation is thought to proceed from a single cis-acting switch region or inactivation centre (XIC/Xic). In the human, XIC has been mapped to band Xq13 (ref. 6) and in the mouse to band XD (ref. 7), and comparative mapping has shown that the XIC regions in the two species are syntenic. The recently described human XIST gene maps to the XIC region and seems to be expressed only from the inactive X chromosome. We report here that the mouse Xist gene maps to the Xic region of the mouse X chromosome and, using an interspecific Mus spretus/Mus musculus domesticus F1 hybrid mouse carrying the T(X;16)16H translocation, show that Xist is exclusively expressed from the inactive X chromosome. Conservation between man and mouse of chromosomal position and unique expression exclusively from the inactive X chromosome lends support to the hypothesis that XIST and its mouse homologue are involved in X-chromosome inactivation.