Human Molecular Genetics

We previously have described the detection of presumptive X-linked restriction fragments by Southern analysis of male (XY) and female (XX) genomic DNA with a Uty probe (14). Two mouse embryo cDNA libraries were screened with Uty probes in order to isolate the X-linked transcript, and four overlapping cDNAs were obtained (Fig. 1a). The single, 4001 bp open reading frame (ORF) of the largest Utx cDNA (1E) remains open at the 5' end. We have been unable to isolate more of the transcript by conventional methods such as library screening and RACE-PCR. However, comparison with the ORFs of murine Uty and the recently reported human UTX gene (16) suggests that only some 200 bp of ORF at the 5' end remains to be cloned. The Utx ORF is predicted to encode a member of the TPR protein family (Fig. 1b), exhibiting strong similarity to Uty at the both the nucleotide and amino acid level (Fig. 1c).a

Figure 1. Isolation and characterization of mouse Utx. (a) Isolation of mouse Utx cDNAs. Screening of mouse embryonic cDNA libraries resulted in the isolation of four Utx cDNA clones. The relative positions and sizes of these are indicated. Clones 1C and 1E differ at their 3' termini, diverging at a position (indicated by the broken line in clone 1C) shortly before in-frame stop codons in both clones (marked by asterisks). Clone 1.1N contains an additional 156 bp of sequence (indicated by the triangle) not found in 1E or 4.2. This does not disrupt the ORF. RT-PCR across this region confirms the existence of alternative splicing products (data not shown). The region of clone 1E encoding the TPR domain is boxed. The primers used to study Utx expression (Utx-12, -13) are indicated as arrows. The region of clone 1E corresponding to human EST R64076 is also indicated. (b) Predicted protein sequence of the Utx gene product. The translated 4001 bp ORF of clone 1E is shown. The eight TPR motifs are underlined; the last four are contiguous. Two potential nuclear localization signals (amino acid residues 1005-1008 and 1026-1029, respectively) are shown in italics. (c) Sequence comparison of Uty and Utx. A diagrammatic representation is shown of the alignment of the ORFs of Uty and Utx.The ORFs have been divided into three segments on the basis of their similarity. Segments are as follows: A, Uty nucleotides 39-1395, Utx 1-1146; B, Uty nucleotides 1396-2120, Utx 1147-2414; C, Uty nucleotides 2121-3558, Utx 2415-4001. The nucleotide (nu) identities and amino acid ([alpha][alpha]) similarities are shown above each segment. The region of relative divergence is marked with a bold line. The Utx-specific region (nucleotides 1229-1756) is indicated by a non-aligned segment, and the region corresponding to the TPR domain is marked by a shaded box.

In order to confirm the chromosomal origin of the Utx transcript, a Utx cDNA clone (1.1N) was hybridized to TaqI-digested genomic DNA samples from progeny of an interspecific backcross, previously typed for a range of X-linked markers (17). A single hybridizing fragment was detected, differing in size between the two species [Mus musculus (C57BL/6) = 8.5 kb and Mus spretus = 7.5 kb] (data not shown). Haplotype analysis of 50 backcross progeny mice positions the gene between the X-linked markers DXMit50 (3/50 recombinants, 6 ± 3.3 cM) and DXMit72 (2/50 recombinants, 4 ± 2.8 cM) in the proximal region of the mouse X chromosome (Fig. 2a). In order to obtain a localization with respect to known genes in the proximal region of the mouse X chromosome, segregation of 1.1N was also analysed in 24 interspecific backcross progeny mice already typed for the genes Otc, Ube1x and Hprt and known to harbour recombination breakpoints between them (18). Haplotype analysis of these recombinant mice showed Utx to map between Otc and Ube1x (data not shown). Extrapolating from the two sets of mapping data, Utx can be positioned in a small interval on the mouse X chromosome proximal to Ube1x and distal to marker DXMit72 (Fig. 2b). This interval contains the markers Maoa and Maob,and places Utx in band A2-A3 (19).a

Figure 2. Genetic mapping of Utx on the mouse X chromosome. (a) Haplotype analysis of 50 interspecific backcross animals previously typed for X-linked markers (17). Each solid box represents an M.spretus allele, each open box an M.musculus (C57BL/6) allele. Numbers beneath each column indicate the number of mice in each recombinant class. Minimization of double recombinants suggests a location of Utx between the markers DXMit72 and DXMit50.(b) Genetic map of the mouse X chromosome indicating the relative positions of the DXMit72-DXMit50 interval and the anchor loci Hprt, Ube1X and Otc in the proximal region. The distal segment of the map also shows the position of the two genes previously shown to escape X inactivation in the mouse, Smcx (10) and the pseudoaotosomal gene Sts (12). The distance between Hprt and Plp is ~38 cM (19).

Expression

Reverse-transcriptase polymerase chain reaction (RT-PCR) with Utx-specific primers yielded a product in all male and female tissues tested in 13.5 days post-coitum(dpc) mouse embryos (Fig. 3a). Northern analysis of female mouse poly(A)⁺ RNA samples using cDNA clone 1.1N detected a transcript of 5.0-5.5 kb in several adult tissues (Fig. 3b).

Figure 3. Expression of murine Utx. (a) RT-PCR with Utx-specific primers gives a 460 bp product in every male and female fetal tissue tested. RNA was derived from pooled tissues from 13.5 dpc fetuses (C3H/101 F1 animals). PCR (35 cycles) was performed with total RNA, both with (+) and without (-) reverse transcription, from the following tissues: brain (B), heart (H), lung (N), liver (L), gut (G), forelimb (F), kidney (K), ovary (O) and testis (T). The first track contains markers. (b) Hybridization of Utx clone 1.1N to poly(A)+ RNA from three adult female tissues reveals a transcript of ~5.5 kb. No significant variation in transcript levels is apparent. Loading was controlled by hybridization with a [beta]-actin probe (data not shown). Autoradiographic exposure was for 3 days.

The predicted Utx gene product shows strong similarity to the predicted product of the mouse Uty gene (14). Figure 1c shows an alignment of the ORFs of Utx and Uty, indicating a central region of divergence between the two genes where similarity drops to ~66%, at both the nucleotide and amino acid level. Utx and Uty share strong homology outside of the variant region (Fig. 1c). In addition, a region of ~500 bp of the 4kb Utx ORF appears to have no equivalent in the Uty composite cDNA described (14). RT-PCR employing primers in this region was used to confirm that it is exonic and not a contaminating intron (data not shown). This region is conserved in the human UTX cDNA (16).

Database searches with the Utx sequence identify other members of the TPR protein family, the best match to a gene product of known function being the yeast glucose repressor protein, Ssn6p (20), which acts as a transcriptional repressor. This best match is identical to that previously described for Uty (14).

In order to identify an X-linked human homologue of Utx, primers were designed (hUTX-1 and hUTX-2) from the sequence of a human expressed sequence tag (EST; R64076) which shows 95% identity at the nucleotide level to murine Utx. An RT-PCR product, derived from human female fibroblast cDNA using these primers, was used in Southern analysis of a panel of rodent-human somatic cell hybrids carrying derivative X chromosomes (data not shown).This hybridization analysis indicated a location at Xp11.23-Xp11.3 between the t75-2ma-1b and SIN76 breakpoints (21). To confirm this localization of human UTX, high density cosmid filter arrays from a flow-sorted X chromosome library (22,23) were then screened with mouse cDNA clone 4.2 (Fig. 1a). A single positive cosmid was isolated and mapped by fluorescent in situ hybridization (FISH) on normal human metaphase spreads to Xp11.2 (data not shown).

A human Y-linked homologue

Southern analysis of male and female human genomic DNA with a murine Uty probe revealed male-specific fragments and fragments shared between males and females (data not shown). Hybridization of this probe to a series of contiguous yeast artificial chromosome (YAC) clones from the human Y chromosome (24) showed strong hybridization to yOX YAC clone 237, indicating a localization of human UTY to band 5D/5E of Yq (data not shown). Recently, UTY was shown to map to band 5C on the basis of deletion mapping (16). Band 5 of Yq is known to contain a gene(s) functioning in spermatogenesis (25) and a Y-specific growth gene (26).

Escape from X inactivation

In order to assay for expression from the inactive mouse X chromosome, females carrying the T(X;16)16H (T16H) translocation were used. As previously described (13,27-29), T16H females undergo non-random inactivation of the normal, paternally derived X chromosome. We exploited two variants between the normal X chromosome, derived from M.castaneus, and the T16H translocation X chromosome in order to assay for expression of Utx from Xi. Utx RT-PCR products derived from parental mice and F1 females carrying the T16H translocation were either analysed by gel electrophoresis (Fig. 4a) or sequenced directly (Fig. 4b). In the case of both variants analysed, the T16H and M.castaneus Utx alleles were detected in F1 T16H females, indicating that Utx escapes X chromosome inactivation in the mouse.

Figure 4. UTX escapes X chromosome inactivation in mice and humans. (a) Negative image of an ethidium bromide-stained gel showing mouse Utx RT-PCR products from brain RNA samples of T(X;16)16H (T16H), M.castaneus (M.CAST) and two newborn (T16H*M.castaneus) F1 females. F1 females bearing the T16H translocation show non-random inactivation of the paternally derived M.castaneus X chromosome. RT-PCR was performed with (+) and without (-) reverse transcriptase to control for genomic DNA contamination. `D' is a genomic DNA control. Expression of both the T16H and M.castaneus Utx alleles is observed in the F1 carrier females, establishing that Utx is expressed from the inactive X chromosome. The control Hprt gene shows a non-random pattern of inactivation, as expected. Primers Utx-4 and Utx-5 were used for the first 20 cycles of amplification, and nested primers Utx-6 and Utx-7 were then employed for an additional 15 cycles on an aliquot of the first-round product. Products were digested with BstEII to distinguish between the parental alleles.The control gene, Hprt, was amplified and alleles differentiated by HinfIdigestion as previously described (29). (b) Direct sequence analysis of Utx RT-PCR products from tissues of a T(X;16)16H female, an M.castaneus male (M.CAST) and a (T16H*M.castaneus)F1 female. Direct sequence analysis of Utx RT-PCR products from two tissues (kidney and brain) of an F1 female T16H carrier shows them to consist of a mixture of products derived from both the T16H allele and the M.castaneus allele. These data confirm the expression of Utx from the mouse Xi. Primers Utx-12 and Utx-13, which give no amplification product with genomic DNA template, were used for RT-PCR and Utx-15 for sequencing. Analysis of the expression of two control genes, Hprt and Xist, established that non-random X-inactivation had occurred in these F1 tissues (data not shown). (c) Negative image of ethidium bromide-stained gels showing RT-PCR amplification of human UTX and PGK1 from a range of mouse-human somatic cell hybrids. Lanes 1 and 2 are control lanes showing amplification of UTX from human (H) and mouse (M) cDNA. Lanes 3 and 4 are from the mouse-human somatic cell hybrids t60-12 (lane 3) and AHA-11aB1 (lane 4), both of which contain an active human X chromosome on a mouse background. Somatic cell hybrids containing an inactive human X chromosome are t86-B1maz1b-3a (lane 5), t75-2maz34-4a (lane 6), t48-1a-1DAZ4A (lane 7), t11-4Aaz5 (lane 8) and LT23-1E2Buv5Cl26-7A2 (lane 9). UTX is expressed from both the active and inactive X chromosome, whilst PGK1 shows expression only from the two hybrids containing an active X. The X chromosomal origin of the hUTX-1/2 product was also confirmed by amplification from cell hybrids AHA11aB1, t60-12 and LT23-1E2Buv5Cl26-7A2, which retain an X chromosome as their only human chromosome (lanes 3, 4 and 9). The low molecular weight product in PGK1 tracks 6-8 is likely to be primer dimer.

To determine whether the human UTX gene was expressed from the inactive X chromosome, RT-PCR using the hUTX primers described above was employed. A series of mouse-human somatic cell hybrids that retain independent active or inactive X chromosomes (30) were analysed for UTX expression. As shown in Figure 4c, the control gene PGK1 is subject to inactivation, and although PGK1 is expressed in the two hybrids carrying active human X chromosomes, no expression was seen in any of the five independent hybrids retaining inactive X chromosomes. In contrast, UTX expression was observed in both active and inactive X hybrids, demonstrating that the human gene escapes X inactivation. These data confirm the recent report of UTX expression from human Xi (16).

DISCUSSION

We have identified and characterized an X-linked gene which escapes X chromosome inactivation in both mice and humans. In mice, Utx is only the second gene from the X-specific portion of the X chromosome known to be expressed from the inactive X (Xi), the other being Smcx (10,11,29,31). In contrast, its human counterpart UTX is an addition to an already long list of genes which are expressed from human Xi (9,32).

The existence of human genes that escape X chromosome inactivation is widely believed to explain the 45,X Turner syndrome phenotype. Such X-linked `Turner' genes are predicted to have a functionally equivalent Y-linked homologue (7,8). Thus in 46,XX and 46,XY individuals, a normal phenotype would result from an effective double dose of each of these genes, whilst in 45,X individuals, haploinsufficiency would result in death in utero or characteristic Turner stigmata in survivors. While several candidates have been proposed, including the recently identified SHOX gene (33), the gene(s) responsible for Turner syndrome have not been identified. UTX maps to a region of the human X chromosome (Xp11-22) associated with Turner syndrome in females bearing interstitial deletions (3) and escapes X chromosome inactivation. Whilst it is not yet known whether its Y-linked homologue UTY is functionally equivalent, the potential role of UTX in Turner syndrome should be investigated further.

The functional equivalence of UTX and UTY can be addressed directly in the mouse by targeted mutagenesis. Mouse Utx and Uty show strong overall homology, but the central region of divergence between the two could reflect either a lower requirement for structural conservation in this region or functional non-equivalence between the two proteins and a male-specific role for Uty.Comparison of the phenotype of males with females bearing one allele of Utx inactivated by homologous recombination should determine whether Uty or some other loci can function in the place of Utx. These experiments will also determine whether haploinsufficiency of Utx contributes to any of the phenotypic characteristics of the XO mouse, such as its reduced ability to support the survival and prenatal growth of embryos (6,34).

Differences in phenotype between 45,X humans and XO mice have been attributed to an absence of X-specific mouse genes escaping X inactivation (13). However, it is now clear that at least two such genes exist. Localized areas of persistent histone H4 acetylation have been detected on both mouse and human Xi, identifying three homologous chromosomal areas with potential transcriptional competence (35). UTX maps to one of these homologous regions: Xp11.2 in humans and band A2 in the mouse (Fig. 2). It will be interesting to determine whether these regions contain other genes escaping X chromosome inactivation, particularly on the mouse X chromosome.

Whilst the PCR experiments employed to assay expression of Utx from the inactive mouse X chromosome were not designed to be quantitative, expression from the active X chromosome appears to exceed that from Xi (Fig. 4a and b). This observation is similar to that originally described for the expression of Smcx from the mouse Xi (10), which was confirmed by quantitative procedures (29,31).It will now be possible to determine whether the stage and tissue specificity which characterize the degree of escape from X inactivation by the murine Smcx gene (29,31) are common to Smcx and Utx, or whether genes active on Xi exhibit unique dynamics of expression. This will allow further insight into the mechanism of spread of inactivation along the X chromosome and the functional significance of the escape of murine X-linked genes from this process.

MATERIALS AND METHODS

Primers hUTX-1 and hUTX-2 preferentially amplify the human UTX gene, though a faint product from mouse of the same size was also observed. Sequence analysis of this mouse transcript identified several nucleotide differences when compared with the human gene. Therefore, to analyse expression specifically from the human X chromosome in somatic cell hybrids, RT-PCR products were digested with HinfI to cleave the mouse product, and a 299 bp human-specific product remains. To confirm further that the product was human in origin, the products amplified from two somatic cell hybrids containing independent inactive X chromosomes were sequenced and shown to be identical to the human X-linked EST R64076.

ACKNOWLEDGEMENTS

We acknowledge J.M.Dunn for technical assistance. We wish to thank Graham Kay, Yvonne Boyd and Steve Brown for useful discussions, Neil Brockdorff for providing interspecific backcross mouse genomic DNA for mapping, and K.E.Davis for fluorescent in situ hybridization. We also thank Mandy Spurdle for supplying a copy of the human Y chromosome yOX YAC contig collection. This work was supported by a grant from the Australian Research Council to P.K. C.P. and A.P.M. were funded by the Wellcome Trust.

REFERENCES

2. Turner, H.H. (1938) A syndrome of infantilism, congenital webbed neck, and cubitus valgus. Endocrinology, 23,566-574.

3. Ogata, T. and Matsuo, N. (1995) Turner syndrome and female sex chromosome aberrations: deduction of the principal factors involved in the development of clinical features. Hum. Genet.,95,607-629.

4. Searle, A.G. (1990) In Lyon, M.F. (ed.), Genetic Variants and Strains of the Laboratory Mouse. 2nd edn. Oxford University Press, Oxford, pp. 583-586.

5. Burgoyne, P.S. and Baker T.G. (1985) Perinatal oocyte loss in XO mice and its implications for the aetiology of gonadal dysgenesis in XO women. J. Reprod. Fertil., 75,633-645. MEDLINE Abstract

6. Hunt, P.A. (1991) Survival of XO mouse fetuses: effect of parental origin of the X chromosome or uterine environment. Development, 111,1137-1141. MEDLINE Abstract

7. Ferguson-Smith, M.A. (1965) Karyotype-phenotype correlations in gonadal dysgenesis and their bearing on the pathogenesis of malformations. J. Med. Genet., 2,142-155.

8. Zinn, A.R., Page, D.C. and Fisher, E.M.C. (1993) Turner syndrome: the case of the missing sex chromosome. Trends Genet.,9,90-93. MEDLINE Abstract

9. Brown, C.J., Carrel, L. and Willard, H.F. (1997) Expression of genes from the human active and inactive X chromosomes. Am. J. Hum. Genet., 60,1333-1343. MEDLINE Abstract

10. Agulnik, A.I., Mitchell, M.J., Mattei, M.-G., Borsani, G., Avner, P.A., Lerner, J.L. and Bishop C.E. (1994) A novel X gene with a widely transcribed Y-linked homologue escapes X-inactivation in mouse and human. Hum. Mol. Genet., 3,879-884. MEDLINE Abstract

11. Wu, J., Salido, E.C., Yen, P.H., Mohandas, T.K., Heng, H.H., Tsui, L.C., Park, J., Chapman, V.M. and Shapiro, L.J. (1994) The murine Xe169 gene escapes X-inactivation like its human homologue. Nature Genet.,7,491-496. MEDLINE Abstract

12. Salido, E.C., Li, X.M., Yen, P.H., Martin, N., Mohandas, T.K. and Shapiro, L.J. (1996) Cloning and expression of the mouse pseudoautosomal steroid sulphatase gene (Sts). Nature Genet., 13,83-86. MEDLINE Abstract

13. Ashworth, A., Rastan, S., Lovell-Badge, R. and Kay, G. (1991) X-chromosome inactivation may explain the difference in viability of XO humans and mice. Nature, 351,406-408. MEDLINE Abstract

14. Greenfield, A.J., Scott, D., Pennisi, D., Ehrmann, I., Ellis, P., Cooper, L., Simpson, E. and Koopman, P. (1996) An H-YDb epitope is encoded by a novel mouse Y chromosome gene. Nature Genet., 14,474-478.

15. Smith, R.L., Redd, M.J. and Johnson, AD. (1995) The tetratricopeptide repeats of Ssn6 interact with the homeodomain of [alpha]2. Genes Dev., 9, 2903-2910. MEDLINE Abstract

16. Lahn, B.T. and Page, D.C. (1997) Functional coherence of the human Y chromosome. Science, 278,675-680. MEDLINE Abstract

17. Cavanna, J.S., Coulton, G., Morgan, J.E., Brockdorff, N., Forrest, S.M., Davies, K.E. and Brown, S.D.M. (1988) Molecular and genetic mapping of the mouse mdx locus. Genomics, 3,337-341. MEDLINE Abstract

18. Kay, G.F., Ashworth, A., Penny, G.D., Dunlop, M., Swift, S., Brockdorff, N. and Rastan, S. (1991) A candidate spermatogenesis gene on the mouse Y chromosome is homologous to ubiquitin-activating enzyme E1. Nature, 354,486-489. MEDLINE Abstract

19. Boyd, Y., Herman, G.E., Avner, P., Disteche, C.M., Adler, D., Reed, V. and Blair, H.J. (1997) Mouse X chromosome. Mammalian Genome, 7,313-326.

20. Keleher, C.A., Redd, M.J., Schultz, J., Carlson, M. and Johnson, A.D. (1992) Ssn6-Tup1 is a general repressor of transcription in yeast. Cell, 68,709-719. MEDLINE Abstract

21. Lafreniere, R.G., Brown, C.J., Powers, V.E., Carrel, L., Davies, K.E., Barker, D.F. and Willard, H.F. (1991) Physical mapping of 60 DNA markers in the p21.1 -> q21.3 region of the human X chromosome. Genomics, 11,352-363. MEDLINE Abstract

22. Lehrach, H., Drmanac, R., Hoheisel, J.D., Larin, Z., Lennon, G., Monaco, A.P. et al. (1991) In Davies, K.E. and Tilghman, S.M. (eds), Genome Analysis. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, Vol. 1, pp. 39-81.

23. Nizetic, D., Zehetner, G., Monaco, A.P., Gellen, L., Young, B.D. and Lehrach, H. (1991) Construction, arraying, and high-density screening of large insert libraries of human chromosomes X and 21: their potential use as reference libraries. Proc. Natl Acad. Sci. USA, 88,3233-3237. MEDLINE Abstract

24. Foote, S., Vollrath, D., Hilton, A. and Page, D.C. (1992) The human Y chromosome: overlapping DNA clones spanning the euchromatic region. Science, 258,60-66. MEDLINE Abstract

25. Vogt, P.H., Edelmann, A., Kirsch, S., Henegariu, O., Hirschmann, P., Kiesewetter, F. et al. (1996) Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11. Hum. Mol. Genet., 5,933-943. MEDLINE Abstract

26. Ogata, T., Tomita, K., Hida, A., Matsuo, N., Nakahori, Y. and Nakagome, Y. (1995) Chromosomal localisation of a Y specific growth gene. J. Med. Genet., 32,572-575. MEDLINE Abstract

27. Takagi, N. (1980) Primary and secondary non-random X chromosome inactivation in early female mouse embryos carrying Searle's translocation T(X;16)16H. Chromosoma,81,439-459. MEDLINE Abstract

28. Carrel, L., Clemson, C.M., Dunn, J.M., Miller, A.P., Hunt, P.A., Lawrence, J.B. and Willard, H.F. (1996) X inactivation analysis and DNA methylation studies of the ubiquitin activating enzyme E1 and PCTAIRE-1 genes in human and mouse. Hum. Mol. Genet.,5,391-401. MEDLINE Abstract

29. Carrel, L., Hunt, P.A. and Willard, H.F. (1996) Tissue and lineage-specific variation in inactive X chromosome expression of the murine Smcx gene. Hum. Mol. Genet., 5,1361-1366. MEDLINE Abstract

30. Willard, H.F., Brown, C.J., Carrel, L., Hendrich, B. and Miller, A.P. (1993) Epigenetic and chromosomal control of gene expression: molecular and genetic analysis of X chromosome inactivation. Cold Spring Harbor Symp. Quant. Biol., 58,315-322. MEDLINE Abstract

31. Sheardown, S., Norris, D., Fisher, A. and Brockdorff, N. (1996) The mouse Smcx gene exhibits developmental and tissue-specific variation in degree of escape from X inactivation. Hum. Mol. Genet., 5,1355-1360. MEDLINE Abstract

32. Disteche, C.M. (1995) Escape from X inactivation in human and mouse. Trends Genet., 11,17-22. MEDLINE Abstract

33. Rao, E., Weiss, B., Fukami, M., Rump, A., Niesler, B., Mertz, A. et al. (1997) Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome. Nature Genet., 16,54-63. MEDLINE Abstract

34. Banzai, M., Omoe, K., Ishikawa, H. and Endo, A. (1995) Viability, development and incidence of chromosome anomalies of preimplantation embryos from XO mice. Cytogenet. Cell Genet.,70,273-277. MEDLINE Abstract

35. Jeppesen, P. and Turner, B.M. (1993) The inactive X chromosome in female mammals is distinguished by a lack of histone H4 acetylation, a cytogenetic marker for gene expression. Cell, 74,281-289. MEDLINE Abstract

36. Sambrook, J., Fritsch, E. and Maniatis, T. (1989) Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.

37. Jeske, Y.W.A., Bowles, J., Greenfield, A. and Koopman, P. (1995) Expression of a linear Sry transcript in the mouse genital ridge. Nature Genet., 10,480-482.

*To whom correspondence should be addressed. Tel: +44 1235 824 544; Fax: +44 1235 834 776; Email: a.greenfield@har.mrc.ac.uk
Present addresses: ⁺Laboratoire de Génétique Médicale, CHU, Allée du Morvan, 54511 Vandoeuvre les Nancy cedex, France and ^[dagger]Telethon Institute of Genetics and Medicine, San Raffaele Biomedical Science Park, Milan, Italy

CiteULike

Connotea

Del.icio.us

This article has been cited by other articles:

				P. A.C. Cloos, J. Christensen, K. Agger, and K. Helin Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease Genes & Dev., May 1, 2008; 22(9): 1115 - 1140. [Abstract] [Full Text] [PDF]

				J. Xu, X. Deng, R. Watkins, and C. M. Disteche Sex-Specific Differences in Expression of Histone Demethylases Utx and Uty in Mouse Brain and Neurons J. Neurosci., April 23, 2008; 28(17): 4521 - 4527. [Abstract] [Full Text] [PDF]

				E. R. Smith, M. G. Lee, B. Winter, N. M. Droz, J. C. Eissenberg, R. Shiekhattar, and A. Shilatifard Drosophila UTX Is a Histone H3 Lys27 Demethylase That Colocalizes with the Elongating Form of RNA Polymerase II Mol. Cell. Biol., February 1, 2008; 28(3): 1041 - 1046. [Abstract] [Full Text] [PDF]

				S. Hong, Y.-W. Cho, L.-R. Yu, H. Yu, T. D. Veenstra, and K. Ge Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases PNAS, November 20, 2007; 104(47): 18439 - 18444. [Abstract] [Full Text] [PDF]

				I. Issaeva, Y. Zonis, T. Rozovskaia, K. Orlovsky, C. M. Croce, T. Nakamura, A. Mazo, L. Eisenbach, and E. Canaani Knockdown of ALR (MLL2) Reveals ALR Target Genes and Leads to Alterations in Cell Adhesion and Growth Mol. Cell. Biol., March 1, 2007; 27(5): 1889 - 1903. [Abstract] [Full Text] [PDF]

				P. J. Wang, D. C. Page, and J. R. McCarrey Differential expression of sex-linked and autosomal germ-cell-specific genes during spermatogenesis in the mouse Hum. Mol. Genet., October 1, 2005; 14(19): 2911 - 2918. [Abstract] [Full Text] [PDF]

				D. B. Miklos, H. T. Kim, K. H. Miller, L. Guo, E. Zorn, S. J. Lee, E. P. Hochberg, C. J. Wu, E. P. Alyea, C. Cutler, et al. Antibody responses to H-Y minor histocompatibility antigens correlate with chronic graft-versus-host disease and disease remission Blood, April 1, 2005; 105(7): 2973 - 2978. [Abstract] [Full Text] [PDF]

				A. R. Isles, W. Davies, D. Burrmann, P. S. Burgoyne, and L. S. Wilkinson Effects on fear reactivity in XO mice are due to haploinsufficiency of a non-PAR X gene: implications for emotional function in Turner's syndrome Hum. Mol. Genet., September 1, 2004; 13(17): 1849 - 1855. [Abstract] [Full Text] [PDF]

				M. L. Jison, P. J. Munson, J. J. Barb, A. F. Suffredini, S. Talwar, C. Logun, N. Raghavachari, J. H. Beigel, J. H. Shelhamer, R. L. Danner, et al. Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease Blood, July 1, 2004; 104(1): 270 - 280. [Abstract] [Full Text] [PDF]

				P. A. Fowler, T. Sorsa-Leslie, P. Cash, B. Dunbar, W. Melvin, Y. Wilson, H. D. Mason, and W. Harris A 60-66 kDa protein with gonadotrophin surge attenuating factor bioactivity is produced by human ovarian granulosa cells Mol. Hum. Reprod., September 1, 2002; 8(9): 823 - 832. [Abstract] [Full Text] [PDF]

				J. Xu, P. S. Burgoyne, and A. P. Arnold Sex differences in sex chromosome gene expression in mouse brain Hum. Mol. Genet., June 1, 2002; 11(12): 1409 - 1419. [Abstract] [Full Text] [PDF]

				M. H. J. Vogt, E. Goulmy, F. M. Kloosterboer, E. Blokland, R. A. de Paus, R. Willemze, and J. H. F. Falkenburg UTY gene codes for an HLA-B60-restricted human male-specific minor histocompatibility antigen involved in stem cell graft rejection: characterization of the critical polymorphic amino acid residues for T-cell recognition Blood, November 1, 2000; 96(9): 3126 - 3132. [Abstract] [Full Text] [PDF]

This Article Abstract FREE Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Search for citing articles in: ISI Web of Science (46) Request Permissions Google Scholar Articles by Greenfield, A. Articles by Koopman, P. Search for Related Content PubMed PubMed Citation Articles by Greenfield, A. Articles by Koopman, P. Social Bookmarking          What's this?