Cytogenetic and molecular studies on a recombinant human X chromosome: implications for the spreading of X chromosome inactivation.

Mohandas, T.; Geller, Robin L.; Yen, Pauline H.; Rosendorff, Jennifer; Bernstein, R; Yoshida, Akira; Shapiro, Larry J.

doi:10.1073/pnas.84.14.4954

Cited by 53 publications

(35 citation statements)

References 36 publications

(31 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The paternally derived Pgk-1 gene is preferentially inactivated along with all other X-linked genes in extraembryonic tissues of female embryos; however, the paternally derived Pgk-lac2 transgene was expressed in extra-embryonic tissues of all transgenic embryos, suggesting that the transgene does not carry sequences that can be imprinted to mediate paternal-specific inactivation. These results are consistent with studies of X-autosome translocations (Rastan, 1983;Mohandas et al, 1987) that suggest that inactivation of a n X-linked gene requires that it be linked to the region of the X chromosome from which inactivation is thought to be initiated.…”

Section: Discussionsupporting

confidence: 91%

Murine PGK‐1 promoter drives widespread but not uniform expression in transgenic mice

McBurney

Staines

Boekelheide

et al. 1994

Developmental Dynamics

View full text Add to dashboard Cite

Pgk-1 is an X-linked gene encoding 3-phosphoglycerate kinase, an enzyme necessary in every cell for glycolysis. The regulatory sequences of the Pgk-1 gene were used to drive the E. coli lac2 reporter gene and 2 strains of transgenic animals created with this P g k -l a d transgene carried on autosomes. The levels of expression of Pgk-1 varied from one adult tissue to another and the transgene was similarly regulated. However, in situ staining of the P-galactosidase encoded by the transgene indicated extensive cell-to-cell variability in its level of expression. A reproducible subset of cells stained darkly for the transgene product. Some of these 6-galactosidase positive cells were rapidly proliferating while others appeared to be metabolically very active, suggesting that the Pgk-1 promoter is regulated so as to be more active in cells requiring high levels of glycolysis. Although Pgk-1 is X-linked and subject to X chromosome inactivation, the transgenes were not inactivated in either female somatic or male germ cells. Thus, the Pgk-1 promoter drives transgene expression in all tissues but the levels of expression are not uniform in each cell. o

show abstract

Section: Discussionsupporting

confidence: 91%

Murine PGK‐1 promoter drives widespread but not uniform expression in transgenic mice

McBurney

Staines

Boekelheide

et al. 1994

Developmental Dynamics

View full text Add to dashboard Cite

show abstract

“…These cases are presumed to be the result of either a recombination event in a parent carrying a pericentric inversion [23][24][25][26][27] or inherited from a phenotypically normal mother carrying the abnormal X. 28 We report two additional cases in which an Xq duplication encompassing MECP2 was accompanied by an Xp deletion, resulting from a specific intrachromosomal rearrangement in which the duplicated segment of Xq was translocated to the Xp22.3 band.…”

Section: Xp-xq Rearrangementsmentioning

confidence: 99%

“…The pregnancy was complicated by influenza associated with dehydration. Literature (n¼5) [21][22][23] Literature (n¼8) [25][26][27][28] …”

Section: Casementioning

confidence: 99%

MECP2 duplications in six patients with complex sex chromosome rearrangements

et al. 2010

View full text Add to dashboard Cite

Duplications of the Xq28 chromosome region resulting in functional disomy are associated with a distinct clinical phenotype characterized by infantile hypotonia, severe developmental delay, progressive neurological impairment, absent speech, and proneness to infections. Increased expression of the dosage-sensitive MECP2 gene is considered responsible for the severe neurological impairments observed in affected individuals. Although cytogenetically visible duplications of Xq28 are well documented in the published literature, recent advances using array comparative genomic hybridization (CGH) led to the detection of an increasing number of microduplications spanning MECP2. In rare cases, duplication results from intrachromosomal rearrangement between the X and Y chromosomes. We report six cases with sex chromosome rearrangements involving duplication of MECP2. Cases 1-4 are unbalanced rearrangements between X and Y, resulting in MECP2 duplication. The additional Xq material was translocated to Yp in three cases (cases 1-3), and to the heterochromatic region of Yq12 in one case (case 4). Cases 5 and 6 were identified by array CGH to have a loss in copy number at Xp and a gain in copy number at Xq28 involving the MECP2 gene. In both cases, fluorescent in situ hybridization (FISH) analysis revealed a recombinant X chromosome containing the duplicated material from Xq28 on Xp, resulting from a maternal pericentric inversion. These cases add to a growing number of MECP2 duplications that have been detected by array CGH, while demonstrating the value of confirmatory chromosome and FISH studies for the localization of the duplicated material and the identification of complex rearrangements.

show abstract

“…Analysis of expression of X-linked markers in somatic cell hybrids that retained the rearranged X in its inactive state revealed that MIC2 and STS were expressed. G6PD, however, was not expressed, presumably as a consequence of normal inactivation of both copies of the gene (38). The observation that X chromosome material can be inactivated on both sides of a segment that is active is compelling evidence that differences in gene or chromosome organization necessary for escape from inactivation must exist.…”

mentioning

confidence: 82%

“…It is possible that some intrinsic difference in gene organization accounts for escape of MIC2 from X-inactivation. Mohandas et al (38) described a rearranged X chromosome in which a duplicated segment Xq26.3-Xqter is distal to MIC2 and STS on the tip of the chromosome short arm. The duplicated material includes G6PD locus.…”

mentioning

confidence: 99%

Absence of methylation of a CpG-rich region at the 5' end of the MIC2 gene on the active X, the inactive X, and the Y chromosome.

Goodfellow

Mondello

Darling

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

We have identified and characterized a Hpa II tiny fragment (HTF) island associated with the promoter region of the pseudoautosomal gene MIC2. The MIC2 HTF island is unmethylated on both the active and inactive X chromosome and is similarly unmethylated on the Y chromosome. Unlike the majority of genes borne on the X chromosome, MIC2 fails to undergo X chromosome inactivation. HTF islands associated with X chromosome-linked genes that are inactivated are highly methylated on the inactive or transcriptionally silent homologue. The failure of MIC2 to undergo X chromosome inactivation correlates with the lack of methylation of the HTF island at the 5' end of the gene. These results provide further evidence that DNA methylation plays an important role in the phenomenon of X chromosome inactivation.

show abstract

Cytogenetic and molecular studies on a recombinant human X chromosome: implications for the spreading of X chromosome inactivation.

Cited by 53 publications

References 36 publications

Murine PGK‐1 promoter drives widespread but not uniform expression in transgenic mice

Murine PGK‐1 promoter drives widespread but not uniform expression in transgenic mice

MECP2 duplications in six patients with complex sex chromosome rearrangements

Absence of methylation of a CpG-rich region at the 5' end of the MIC2 gene on the active X, the inactive X, and the Y chromosome.

Contact Info

Product

Resources

About