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Background  The transcriptional silencing of one X chromosome in eutherians requires transcription of the long non-coding RNA gene,  XIST . Many regulatory elements have been identified downstream of the mouse  Xist  gene, including the antisense  Tsix  gene. However, these elements do not show sequence conservation with humans, and the human  TSIX  gene shows critical differences from the mouse. Thus we have undertaken an unbiased identification of regulatory elements both downstream and upstream of the human  XIST  gene using DNase I hypersensitivity mapping.    Results  Downstream of  XIST  a single DNase I hypersensitive site was identified in a mouse undifferentiated ES cell line containing an integration of the human  XIC  region. This site was not observed in somatic cells. Upstream of  XIST , the distance to the flanking  JPX  gene is expanded in humans relative to mice, and we observe a hypersensitive site 65 kb upstream of  XIST , in addition to hypersensitive sites near the  XIST  promoter. This -65 region has bi-directional promoter activity and shows sequence conservation in non-rodent eutheria.    Conclusions  The lack of regulatory elements corresponding to human  TSIX  lends further support to the argument that  TSIX  is not a regulator of  XIST  in humans. The upstream hypersensitive sites we identify show sequence conservation with other eutheria, but not with mice. Therefore the regulation of  XIST  seems to be different between mice and man, and regulatory sequences upstream of  XIST  may be important regulators of  XIST  in non-rodent eutheria instead of  Tsix  which is critical for  Xist  regulation in rodents.

Identification of regulatory elements flanking human XIST reveals species differences