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Human Molecular Genetics Pages 1323-1327

XIST expression from the maternal X chromosome in human male preimplantation embryos at the blastocyst stage
Introduction
Results
Discussion
Materials And Methods
   Human oocytes and embryos
   Reverse transcription
   Polymerase chain reaction
Acknowledgements
References

XIST expression from the maternal X chromosome in human male preimplantation embryos at the blastocyst stage

XIST expression from the maternal X chromosome in human male preimplantation embryos at the blastocyst stage Pierre F. Ray+, Robert M. L. Winston and Alan H. Handyside*

Institute of Obstetrics and Gynaecology, Royal Postgraduate Medical School, Hammersmith Hospital, London W12 0NN, UK

Received March 20, 1997; Revised and Accepted May 28, 1997

In the somatic cells of female mammals, either the maternally or paternally derived X chromosome (XM or XP) is randomly inactivated to achieve dosage compensation for X-linked genes. In early mouse development, however, selective inactivation of XP occurs first in extraembryonic lineages at the blastocyst stage around the time of implantation before later random inactivation in the embryonic ectoderm from which the fetus is derived. Xist, a gene mapping to the X-inactivation centre (Xic), is exclusively expressed from the inactive X-chromosome and is thought to be involved in the initiation of X-inactivation. Consistent with this, Xist is first expressed at the 4-to 8-cell stages, prior to functional inactivation at the blastocyst stage, exclusively from XP in female embryos. This also suggests that genomic imprinting may influence the earliest expression of Xist resulting in selective inactivation of XP and a candidate methylation site in the promoter region has recently been described. Here we report the expression of the human homologue, XIST, in human preimplantation embryos from the 5- to 10-cell stage onwards consistent with its role in the initiation of inactivation. In contrast to the mouse, however, transcripts were detected in both male and female embryos demonstrating XIST expression from the XM in male embryos (XMY).

INTRODUCTION

In the somatic cells of female mammals, dosage compensation for X-linked genes between XX females and XY males is achieved by transcriptional inactivation of genes on one of the two X chromosomes (1 ). Random inactivation of either the maternally or paternally derived X chromosome (XM or XP) occurs early in development and is subsequently stably inherited. Maintenance of inactivation involves heterochromatization characterised by delayed replication late in S phase (2 -4 ), histone H4 deacetylation and methylation of CpG islands (5 -7 ). Transcripts for the Xist gene in the mouse and the human homologue, XIST, are exclusively expressed from the inactive X chromosome (8 ,9 ) and the genes map to the X-inactivation centre (Xic), a region known to mediate X inactivation (10 ). Furthermore, Xist expression in the mouse has been demonstrated to be necessary for X inactivation to occur (11 ).

In the mouse, X-inactivation is first detected at the late morula/blastocyst stages of preimplantation development (12 ,13 ) restricted to the extraembryonic lineages in which XP is selectively inactivated (14 ,15 ). Random inactivation of the XM or XP occurs later in the embryonic ectoderm lineage, and this pattern is maintained in adult somatic tissues. Consistent with a role in the initiation of inactivation, Xist transcripts are first detected in mouse embryos before functional X-inactivation at the 4-cell stage and exclusively from XP suggesting that imprinting may be involved in repressing the initial expression of XM. We demonstrate here that expression of XIST is also detectable in human preimplantation embryos from the 5- to 10-cell stage onwards. In contrast to the mouse, however, transcripts were detected in both male and female embryos indicating expression from XM in the males.

RESULTS

Individual or pooled human oocytes, which had failed to fertilize following in vitro fertilization (IVF), and normally fertilized embryos at various stages of preimplantation development in vitro were lysed and reverse transcription PCR (RT-PCR) used to detect specific transcripts. The cDNA from each sample was split and analysed separately for XIST, ZFX/ZFY and HPRT expression. ZFX and ZFY transcripts from the respective genes on the X and Y chromosomes were amplified with a single set of primers and distinguished by restriction digestion to identify the sex of individual embryos (17 ). HPRT transcripts and omission of reverse transcriptase were used as positive and negative controls, respectively. In each case nested PCR was used to improve the sensitivity and primers designed to span introns to eliminate spurious results from genomic DNA. The XIST primers spanned exons 5, 6i and 6 (Fig. 1 ).


Figure 1. (a) Structure of the XIST cDNA and differential splicing patterns as described in ref. 32. (b) Details of the amplified region and location of the nested primers.

Table 1 . Stage specific XIST expression in pooled human embryos
Stage/day post
insemination		 No. of samples
analysed		 No. of embryos
in each sample		 No. of samples
expressing XIST		 No. of samples
expressing HPRT
Failed fertilized 3 5-9 0 3
2 3 5-10 0 3
3 5 2-10 3 4
4 1 15 1 1
6 3 5-6 3 -

Table 2 XIST expression in single human embryos
Day post
insemination

 No. of embryos
analysed

 No. of positive
samplesa 		No. of embryos expressing a specific transcript
(no. of embryos analysedb)
      XIST HPRT ZFX only ZFX/ZFY
3 12 6 3 (6) 3 (6) 4 (6) 0 (6)
4 6 5 3 (5) 4 (5) 2 (4) 0 (4)
5-6 27 23 23 (23) 11 (12) 14 (21) 5 (21)
Total 45 34 29 (32) 18 (23) 20 (31) 5 (31)
aSamples in which at least one of the four transcripts were detected.
bOnly embryos in which at least one transcript was detected, comfirming reverse transcription, are included.

XIST transcripts were not detectable in pooled failed fertilized oocytes or embryos 2 days post insemination (day 2) (Table 1 ; Fig. 2 ). On day 3, however, XIST transcripts were detected in three of four samples positive for reverse transcription and on subsequent days, up to the blastocyst stage on day 6, were detected in all four samples. This pattern of expression was similar in embryos analysed individually (Table 2 ). On day 3, PCR products for at least one of the transcripts were only detected in six of 12 samples. Three of these were positive for XIST and ZFX transcripts were detected in four. At the blastocyst stage on days 5-6, 23 of 27 samples were positive for at least one of the transcripts which included XIST in every case. Only five of these embryos showed ZFY expression indicating they were XY males but in each of these XIST was also expressed. The presence of alternatively spliced transcripts in which exon 6i was omitted were observed in most of the samples (Fig. 2 ). No amplification products were detected in any of the 68 reverse transcription negative controls analysed. The use of nested PCR prevented any quantitative assessment of XIST expression in male and female embryos at different stages. The consistently strong amplification, however, suggests that it is unlikely that only low levels of transcripts, which may be of no functional significance, are being detected.


Figure 2.XIST, HPRT and ZFX/ZFY transcripts detected by RT-PCR of pooled and individual human oocytes and embryos. Top panel: XIST transcripts are not detectable in pooled failed fertilized and day 2 embryos (2-4-cell stage) but are present in one of the two pooled samples on day 3 (5-16-cell stage), in a pooled sample on day 4, and in four out of five single blastocysts. On day 3, only the full length product (151 bp) is detected, whereas on day 4 and with the single blastocysts both full length and truncated products (95 bp), predicted by the splicing out of exon 6i are present (Fig. 1). Middle panel: HPRT RT-PCR was used as positive control for reverse transcription. In all samples except one single blastocyst, HPRT trancripts (226 bp) were detected confirming successful reverse transcription. In the blastocyst which failed to amplify HPRT, amplification of XIST and ZFX/ZFY also failed indicating a failure of reverse transcription. Bottom panel: ZFX/ZFY trancripts were amplified to identify the sex of individual blastocysts. Following digestion with ClaI the amplified fragment from ZFX remains undigested (357 bp) whereas the ZFY product is cut and yields fragments of 204 and 153 bp. The presence of ZFY transcripts is clearly demonstrated in one of the four single blastocysts expressing XIST, indicating that this embryo is male. Amplification products were only detected in reverse transcription positive samples (+), and never in the reverse transcription negative controls (-). M, molecular weight marker, pBR322 digested with HhaI.

DISCUSSION

The expression of XIST as early as the 5-10-cell stage on day 3 is similar to the mouse in which expression of Xist was first detected at the 4-cell stage (16 ). In contrast to the mouse, however, XIST expression in a high proportion of embryos at all stages and in five blastocysts positively identified as males by the simultaneous detection of ZFY transcripts indicates that expression can occur from XM in males. The low proportion of embryos identified as males probably relates to the difficulty of detecting ZFY transcripts in individual embryos against a high background of ZFX transcripts inherited from the oocyte (17 ). However, all 23 individual blastocysts on days 5-6 in which the RT-PCR was successful showed strong expression and any unidentified males must therefore have also been expressing XIST. We were unable to distinguish expression from XP or XM in female embryos so we cannot conclude that expression is biallelic in these embryos. However, it seems unlikely that XIST would be exclusively expressed from XM.

In the mouse, imprinting of Xist is thought to predetermine early expression and selective inactivation of XP in extraembryonic lineages before the imprint is erased in the embryonic ectoderm prior to random inactivation (16 ). Methylation of specific sites in the paternal copy of Xist has been shown to persist even after the global demethylation that occurs in early cleavage and these sites are a candidate for the imprint in the mouse (18 ).In human, there has been conflicting evidence for selective inactivation of XP in extraembryonic components of placental tissue (19 -21 ). Recently RT-PCR analysis of trophoblast cells isolated from chorionic villus samples of female conceptuses demonstrated that only XM is expressed (22 ). However, only two samples were analysed and it is possible that inactivation was skewed or that the number of cells analysed was so small that they were of clonal origin. Also, the methylation status of XIST in sperm and eggs has not been investigated. Expression of XIST from XM in male embryos at the blastocyst stage suggests that if it is imprinted in the human, it does not affect its expression at these stages.

At the blastocyst stage in the mouse, the imprint appears to be erased prior to random Xist expression and X-inactivation at the beginning of gastrulation in a tissue specific order (16 ,23 ,24 ). If XIST is not imprinted or the imprint does not affect expression in the human embryo during preimplantation development, this would explain expression in both male and female embryos and predict that both alleles are expressed in females. This would also explain differences in the effects of various abnormal combinations of Xist/XIST alleles in mouse and human early development. In the mouse, female embryos in which the functional Xist gene is deleted on XP die soon after implantation as a consequence of failure of development of extraembryonic tissues whereas those inheriting the deletion from XM are unaffected (25 ). A similar phenotype is observed with embryos with extra copies of XM (XMXMXP and XMXMY) presumably as a result of a failure to inactivate the extra XM in the extraembryonic lineages due to imprinted repression of XM Xist alleles (26 ). In contrast human XXX females and males with Klinefelter syndrome (XXY) develop relatively normally despite inheriting a supernumerary XM in a majority of cases (27 ).

A low level of Xist expression has been detected from XM in undifferentiated male mouse embryo stem (ES) cells and from both active X chromosomes in female cells which reverted to the normal pattern of expression exclusively from the inactive X chromosome in female cells on differentiation in vitro (28 ). It will be important therefore to quantify expression in early human embryos to determine the level of expression at these early stages and indeed to compare the levels of expression in males and females. Because nested PCR is necessary to detect transcripts in the very small amount of total mRNA in individual oocytes and embryos, conventional semi-quantitative approaches are not possible. However, since pooled oocytes and embryos on day 2 showed no expression, we consider it unlikely that we are simply detecting `leaky' transcription at the later stages. To examine the possibility that imprinting may not play a role in XIST expression and the initiation of X-inactivation in the human embryo, therefore, will require more direct approaches which could include analysis of allele-specific polymorphisms (29 ) or polymorphisms closely linked to specific methylation sites (30 ), or alternatively, RNA in situ hybridization (31 ,32 ).

MATERIALS AND METHODS

Human oocytes and embryos

Surplus oocytes and embryos were donated for research by couples undergoing IVF treatment with their informed consent. Oocytes were examined 19-20 h post-insemination (day 1) for pronuclei and only normally fertilized two pronucleate embryos were used in this study. Oocytes which failed to fertilize and did not cleave were used after 24 or 48 h. Embryos were cultured in Earles balanced salts solution (EBSS) supplemented with 10% heat inactivated maternal serum. This work was carried out under a Human Fertilisation and Embryology Authority license, with local approval from the Research Ethics Committee of the Royal Postgraduate Medical School.

Reverse transcription

After removing the zona pellucida with acidified Tyrode's solution (pH 2.2) and washing in phosphate buffered saline (PBS) with 4 mg/ml BSA, to remove possible contaminants, individual or pooled oocytes and embryos were lysed in 5 [mu]l of lysis buffer (0.5% NP-40, 10 mM Tris pH 8.0, 10 mM NaCl and 3 mM MgCl2) (33 ). The tubes were immediately plunged into liquid nitrogen prior to storage at -70oC. The lysate was then made up to 19 [mu]l with reverse transcriptase buffer [50 mM Tris-HCl pH 8.3, 75 mM KCl, 3 mM MgCl2, 10 mM DDT (Pharmacia, St Albans, Herts, UK), 300 pmol oligo (dT)12-18 primer (Pharmacia), 0.5 mM dNTP (Pharmacia)]. The mixes were homogenized by pipetting, 5 [mu]l was transferred into a fresh tube for the reverse transcriptase negative control (-) and 1 [mu]l (100 U) of M-MLV reverse transciptase (Gibco, Life Technologies Ltd, Paisley, UK) was added to the remaining 14 [mu]l (+). Both tubes were incubated at 37oC for 2 h and the reaction terminated by heating at 95oC for 5 min.

Polymerase chain reaction

Following reverse transcription, nested PCR was used to detect specific transcripts in 2 [mu]l (HPRT and XIST) and 4 [mu]l (ZFX/ZFY) aliquots of cDNA and reverse transcriptase negative control. PCR was carried out in a final volume of 30 [mu]l containing 10 mM Tris-HCl pH 8.3, 50 mM of each dNTP, 2.5 U Taq polymerase (AmpliTaq, Perkin Elmer, Applied Biosystems, Warrington, Cheshire, UK) and 0.4 [mu]M of each primer, covered with 50 [mu]l of silicone oil and denatured at 95oC for 3 min before thermal cycling. For the second PCR with nested primers, 2 [mu]l of product from the first reaction was transferred to fresh PCR buffer. The primers and cycling conditions for HPRT and ZFX/ZFY were as previously published (34 ,35 ). The outer and inner primers for XIST, annealing to sequences in exons 5 and 6 (Fig. 1 ), were as follows: outer, 5'-CCT ACA AGC AGT GCA GAG AGC-3' and 5'-GAG AAA ATG AGG CAA AGG CA-3' and inner, 5'-TCA GCC TTC CCA CCT GAA G-3' and 5'-AGC AAG AGA AAC ATG GAA ATG G-3'. Thermal cycling at 95oC for 45 s, 60oC for 60 s and 72oC for 60 s with a final extension at 72oC for 5 min was carried out using an Omnigene thermocycler (Hybaid, Teddington, Middlesex, UK) for 30 and 35 cycles for the first and second reactions, respectively.

ZFX/ZFY products were digested with ClaI at 37oC for 2 h. The amplified fragment from ZFX remained undigested (357 bp) whereas the ZFY product was cut and yielded fragments of 204 and 153 bp. RT-PCR products were analysed by gel electrophoresis on 10% polyacrylamide gels at 200 V for 45 min, stained with ethidium bromide and examined with a UV transilluminator (see Fig. 2 ).

ACKNOWLEDGEMENTS

We thank the staff of the Wolson Family Clinic for their collaboration in providing spare embryos and the patients for donating them. The work was funded by the Institute of Obstetrics and Gynaecology Trust Fund, Hammersmith Hospital.

REFERENCES

1 Lyon,M.F. (1961) Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature 190, 372-373.

2 Takagi,N. and Oshimura,M. (1973) Fluorescence and Giemsa banding studies of the allocyclic X chromosome in embryonic and adult mouse cells. Exp. Cell Res.78, 127-135. MEDLINE Abstract

3 Kanda,N. (1981) Selective differential staining of sister chromatids of the facultative heterochromatic X chromosome in the female mouse. Chromosoma 84, 257-263. MEDLINE Abstract

4 Barr,M.L. (1949) A morphological distinction between neurones of male and female, and the behaviour of nucleolar satellites during accelerated nucleoprotein synthesis. Nature 163, 676-677.

5 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

6 Yen,P.H., Patel,P., Chinault,A.C., Mohandas,T. and Shapiro,L.J. (1984) Differential methylation of hypoxanthine phosphoribosyltransferase genes on active and inactive human X chromosomes. Proc. Natl. Acad. Sci. USA 81, 1759-1763. MEDLINE Abstract

7 Wolf,S.F., Dintzis,S., Toniolo,D. et al. (1984) Complete concordance between glucose-6-phosphate dehydrogenase activity and hypomethylation of 3' CpG clusters: implications for X chromosome dosage compensation. Nucleic Acids Res. 12, 9333-9348. MEDLINE Abstract

8 Brown,C.J., Ballabio,.A, Rupert,J.L. et al. (1991) A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature 349, 38-44. MEDLINE Abstract

9 Brockdorff,N., Ashworth,A., Kay,G.F. et al. (1991) Conservation of position and exclusive expression of mouse Xist from the inactive X chromosome. Nature 351, 329-331. MEDLINE Abstract

10 Brown,C.J., Lafreniere,R.G., Powers,V.E. et al. (1991) Localization of the X inactivation centre on the human X chromosome in Xq13. Nature 349, 82-84. MEDLINE Abstract

11 Penny,G.D., Kay,G.F., Sheardown,S.A., Rastan,S. and Brockdorff,N. (1996) Requirement for Xist in X chromosome inactivation [see comments]. Nature 379, 131-137. MEDLINE Abstract

12 Epstein,C.J., Smith,S., Travis,B. and Tucker,G. (1978) Both X chromosomes function before visible X-chromosome inactivation in female mouse embryos. Nature 274, 500-503. MEDLINE Abstract

13 Monk,M. and Harper,M.I. (1979) Sequential X chromosome inactivation coupled with cellular differentiation in early mouse embryos. Nature 281, 311-313. MEDLINE Abstract

14 Takagi,N. and Sasaki,M. (1975) Preferential inactivation of the paternally derived X chromosome in the extraembryonic membranes of the mouse. Nature 256, 640-642. MEDLINE Abstract

15 West,J.D., Frels,W.I., Chapman,V.M. and Papaioannou,V.E. (1977) Preferential expression of the maternally derived X chromosome in the mouse yolk sac. Cell 12, 873-882. MEDLINE Abstract

16 Kay,G.F., Barton,S.C., Surani,M.A. and Rastan,S. (1994) Imprinting and X chromosome counting mechanisms determine Xist expression in early mouse development. Cell 77, 639-650. MEDLINE Abstract

17 Taylor,D.M., Ray,P.F., Ao,A., Winston,R.M.L. and Handyside,A.H. (1997) Paternal transcripts for glucose-6-phosphate dehydrogenase (G6PD) and adenosine deaminase (ADA) are first detectable in the human preimplantation embryo at the 3- to 4-cell stage. Mol. Reprod. Dev. in press.

18 Norris,D.P., Patel,D., Kay,G.F. et al. (1994) Evidence that random and imprinted Xist expression is controlled by preemptive methylation. Cell 77, 41-51. MEDLINE Abstract

19 Ropers,H.H., Wolff,G. and Hitzeroth,H.W. (1978) Preferential X inactivation in human placenta membranes: is the paternal X inactive in early embryonic development of female mammals? Hum. Genet. 43, 265-273. MEDLINE Abstract

20 Migeon,B.R. and Do,T.T. (1979) In search of non-random X inactivation: studies of fetal membranes heterozygous for glucose-6-phosphate dehydrogenase. Am. J. Hum. Genet. 31, 581-585. MEDLINE Abstract

21 Harrison,K.B. (1989) X-chromosome inactivation in the human cytotrophoblast. Cytogenet. Cell Genet.52, 37-41. MEDLINE Abstract

22 Goto,T., Wright,E. and Monk,M. (1997) Paternal X-chromosome inactivation in human trophoblastic cells. Mol. Hum. Reprod. 3, 77-80.

23 Kay,G.F., Penny,G.D., Patel,D., Ashworth,A., Brockdorff,N. and Rastan,S. (1993) Expression of Xist during mouse development suggests a role in the initiation of X chromosome inactivation. Cell 72, 171-182. MEDLINE Abstract

24 Tan,S.S., Williams,E.A. and Tam,P.P. (1993) X-chromosome inactivation occurs at different times in different tissues of the post-implantation mouse embryo. Nature Genet. 3, 170-174. [Published erratum appears in Nature Genet. (1993) 4, 320.]

25 Marahrens,Y., Panning,B., Dausman,J., Strauss,W. and Jaenisch,R. (1997) Xist-deficient mice are defective in dosage compensation but not spermatogenesis. Genes Dev. 11, 156-166. MEDLINE Abstract

26 Tada,T., Takagi,N. and Adler,I.D. (1993) Parental imprinting on the mouse X chromosome: effects on the early development of X0, XXY and XXX embryos. Genet. Res. 62, 139-148. MEDLINE Abstract

27 MacDonald,M., Hassold,T., Harvey,J., Wang,L.H., Morton,N.E. and Jacobs,P. (1994) The origin of 47,XXY and 47,XXX aneuploidy: heterogeneous mechanisms and role of aberrant recombination. Hum. Mol. Genet. 3, 1365-1371. MEDLINE Abstract

28 Panning,B. and Jaenisch,R. (1996) DNA hypomethylation can activate Xist expression and silence X-linked genes. Genes Dev. 10, 1991-2002.

29 Rupert,J.L., Brown,C.J. and Willard,H.F. (1995) Direct detection of non-random X chromosome inactivation by use of transcribed polymorphism in the XIST gene. Eur. J. Hum. Genet. 3, 333-343. MEDLINE Abstract

30 Carrel,L. and Willard,H.F. (1996) An assay for X inactivation based on differential methylation at the fragile X locus, FMR1. Am. J. Med. Genet.64, 27-30. MEDLINE Abstract

31 Clemson,C.M., McNeil,J.A., Willard,H.F. and Lawrence,J.B. (1996) XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure. J. Cell Biol. 132, 259-275. MEDLINE Abstract

32 Brown,C.J., Hendrich,B.D., Rupert,J.L. et al. (1992) The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. Cell 71, 527-542. MEDLINE Abstract

33 Gilliland,G., Perrin,S. and Bunn,H.F. (1990) PCR Protocols: A Guide to Methods and Applications. Academic Press, New York, NY.

34 Chia,C.M., Winston,R.M. and Handyside,A.H. (1995) EGF, TGF-alpha and EGFR expression in human preimplantation embryos. Development 121, 299-307. MEDLINE Abstract

35 Ao,A., Erickson,R.P., Winston,R.M.L. and Handyside,A.H. (1994) Transcription of paternal Y-linked genes in the human zygote as early as the pronucleate stage. Zygote 2, 281-288. MEDLINE Abstract

*To whom correspondence should be addressed at present address: UMDS Department of Obstetrics and Gynaecology, 6th floor North Wing, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK. Tel: +44 171 928 9292; Fax:+44 171 620 12271; Email: a.handyside@umds.ac.uk

+Present address: Department of Biological Sciences, Molecular Biology Program, University of Southern California, Los Angeles, CA 90089-1340, USA

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