Regulatory elements in the minimal promoter region of the mouse Xist gene.
The Xist gene plays a central role in regulating X chromosome inactivation and Xist transcription has recently been shown to be necessary for X inactivation in mouse. We are currently analysing regulation of the Xist gene in order to determine the mechanisms underlying initiation of Xist expression and X inactivation. Sequence comparisons indicate that a region of approximately 0.4 kb upstream of the the major transcriptional start site comprises the Xist minimal promoter. Analysis of reporter constructs demonstrates that the minimal promoter region is active both in embryonic stem (ES) cells and in differentiated derivatives, indicating that sequences either further upstream or downstream are required for appropriate developmental control of Xist transcription. We have examined the minimal promoter region in detail, and in addition to common promoter elements have identified two previously uncharacterised transcription-factor binding sites. Mutation of these sites in reporter constructs indicates that they are functionally important.
Sheardown
S A
SA
X Inactivation Group, MRC Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Newall
A E
AE
Norris
D P
DP
Rastan
S
S
Brockdorff
N
N
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D018983:DNA Footprinting; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D004303:Dosage Compensation, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D017930:Genes, Reporter; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012689:Sequence Homology, Nucleic Acid; D013234:Stem Cells; D035362:Transcription Factor TFIID; D014157:Transcription Factors / Q000235:genetics*; D019473:Transcription Factors, TFII / Q000235:genetics / Q000378:metabolism; D014960:X Chromosome / Q000235:genetics
D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D019473:Transcription Factors, TFII; C077885:XIST non-coding RNA; D008156:Luciferases; C055654:endodeoxyribonuclease NruI; D015252:Deoxyribonucleases, Type II Site-Specific