X-inactivation in female human embryonic stem cells is in a nonrandom pattern and prone to epigenetic alterations.

@article{citeulike:2543959, abstract = {X chromosome inactivation (XCI) is an essential mechanism for dosage compensation of X-linked genes in female cells. We report that subcultures from lines of female human embryonic stem cells (hESCs) exhibit variation (0-100\%) for XCI markers, including XIST RNA expression and enrichment of histone H3 lysine 27 trimethylation (H3K27me3) on the inactive X chromosome (Xi). Surprisingly, regardless of the presence or absence of XCI markers in different cultures, all female hESCs we examined (H7, H9, and HSF6 cells) exhibit a monoallelic expression pattern for a majority of X-linked genes. Our results suggest that these established female hESCs have already completed XCI during the process of derivation and/or propagation, and the XCI pattern of lines we investigated is already not random. Moreover, XIST gene expression in subsets of cultured female hESCs is unstable and subject to stable epigenetic silencing by DNA methylation. In the absence of XIST expression, approximately 12\% of X-linked promoter CpG islands become hypomethylated and a portion of X-linked alleles on the Xi are reactivated. Because alterations in dosage compensation of X-linked genes could impair somatic cell function, we propose that XCI status should be routinely checked in subcultures of female hESCs, with cultures displaying XCI markers better suited for use in regenerative medicine.}, address = {Department of Human Genetics, Geffen School of Medicine, and.}, author = {Shen, Yin and Matsuno, Youko and Fouse, Shaun D D. and Rao, Nagesh and Root, Sierra and Xu, Renhe and Pellegrini, Matteo and Riggs, Arthur D D. and Fan, Guoping }, citeulike-article-id = {2543959}, doi = {10.1073/pnas.0712018105}, issn = {1091-6490}, journal = {Proc Natl Acad Sci U S A}, keywords = {xci-monoallelic}, month = {March}, posted-at = {2008-07-24 17:07:32}, priority = {2}, title = {X-inactivation in female human embryonic stem cells is in a nonrandom pattern and prone to epigenetic alterations.}, url = {http://dx.doi.org/10.1073/pnas.0712018105}, year = {2008} }

TY - JOUR ID - citeulike:2543959 L3 - citeulike-article-id:2543959 TI - X-inactivation in female human embryonic stem cells is in a nonrandom pattern and prone to epigenetic alterations. JF - Proc Natl Acad Sci U S A AD - Department of Human Genetics, Geffen School of Medicine, and. SN - 1091-6490 N2 - X chromosome inactivation (XCI) is an essential mechanism for dosage compensation of X-linked genes in female cells. We report that subcultures from lines of female human embryonic stem cells (hESCs) exhibit variation (0-100%) for XCI markers, including XIST RNA expression and enrichment of histone H3 lysine 27 trimethylation (H3K27me3) on the inactive X chromosome (Xi). Surprisingly, regardless of the presence or absence of XCI markers in different cultures, all female hESCs we examined (H7, H9, and HSF6 cells) exhibit a monoallelic expression pattern for a majority of X-linked genes. Our results suggest that these established female hESCs have already completed XCI during the process of derivation and/or propagation, and the XCI pattern of lines we investigated is already not random. Moreover, XIST gene expression in subsets of cultured female hESCs is unstable and subject to stable epigenetic silencing by DNA methylation. In the absence of XIST expression, approximately 12% of X-linked promoter CpG islands become hypomethylated and a portion of X-linked alleles on the Xi are reactivated. Because alterations in dosage compensation of X-linked genes could impair somatic cell function, we propose that XCI status should be routinely checked in subcultures of female hESCs, with cultures displaying XCI markers better suited for use in regenerative medicine. KW - xci-monoallelic AU - Shen, Yin AU - Matsuno, Youko AU - Fouse, Shaun D AU - Rao, Nagesh AU - Root, Sierra AU - Xu, Renhe AU - Pellegrini, Matteo AU - Riggs, Arthur D AU - Fan, Guoping PY - 2008/03/13/ UR - http://dx.doi.org/10.1073/pnas.0712018105 ER -