Expression data from mouse ES cells after control RNAi (scramble siRNAs) or RNAi specific for Kdm6a treatment.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE45034 | GEO | 2013/03/13
SECONDARY ACCESSION(S): PRJNA192883
REPOSITORIES: GEO
Similar Datasets
Project description:To address the functional role of KDM6A in the regulation of Rhox genes, male and female mouse ES cells were transfected with a mixture of three small interfering RNA duplexes, each of which targets a different region of Kdm6a mRNA. We found that Kdm6a knockdown in mouse ES cells caused a decrease in expression of a subset of Rhox genes, Rhox6 and 9. Furthermore, Rhox6 and 9 expression was decreased in female ES cells but not male ES cells indicating that KDM6A regulates Rhox gene expression in a sexually dimorphic manner. Mouse ES cells were treated by Invitrogen scramble siRNA duplexes or specific siRNA duplexes and used for RNA extraction and hybridization on Affymetrix microarrays. Four RNA samples from two independent double-RNAi treatments and two single-RNAi treatment in undifferentiated female ES cells PGK12.1, and RNA samples from two single-RNAi treatments in undifferentiated male ES cells WD44 were assayed for expression changes by arrays.
2013-03-13 | E-GEOD-45034 | biostudies-arrayexpress
Project description:Here we show binding and occupancy profiles for KDM6A, H3K27me3 and H3K4me3 to address the epigenetic regulation of a subset of Rhox genes, Rhox6 and 9, in female and male ES cells during differentiation. To further address a functional role for KDM6A in the epigenetic regulation of Rhox6 and 9, binding profiles for female ES cells treated with a control siRNA and siRNA specific for Kdm6a are shown. We report that two members of the Rhox cluster, Rhox6 and 9, are regulated by de-methylation of histone H3 at lysine 27 by KDM6A, a histone demethylase with female-biased expression. Our results are consistent with other homeobox genes in that Rhox6 and 9 are in bivalent domains prior to embryonic stem cell differentiation and thus poised for activation. In female mouse ES cells KDM6A is specifically recruited to Rhox6 and 9 for gene activation, a process inhibited by Kdm6a knockdown. In contrast, KDM6A occupancy at Rhox6 and 9 is low in male ES cells and knockdown has no effect on expression. Our study implicates Kdm6a, a gene that escapes X inactivation, in the regulation of genes important in reproduction, suggesting that KDM6A may play a role in the etiology of developmental and reproduction-related effects of X chromosome anomalies. ChIP-chip was used to analyze the binding profiles of KDM6A, H3K27me3, and H3K4me3 during differentiation in female and male ES cells. Additionally, ChiP-chip of KDM6A binding in control treated and siRNA treated ES cells is presented.
2013-03-22 | E-GEOD-45390 | biostudies-arrayexpress
Project description:Here we show binding and occupancy profiles for KDM6A, H3K27me3 and H3K4me3 to address the epigenetic regulation of a subset of Rhox genes, Rhox6 and 9, in female and male ES cells during differentiation. To further address a functional role for KDM6A in the epigenetic regulation of Rhox6 and 9, binding profiles for female ES cells treated with a control siRNA and siRNA specific for Kdm6a are shown. We report that two members of the Rhox cluster, Rhox6 and 9, are regulated by de-methylation of histone H3 at lysine 27 by KDM6A, a histone demethylase with female-biased expression. Our results are consistent with other homeobox genes in that Rhox6 and 9 are in bivalent domains prior to embryonic stem cell differentiation and thus poised for activation. In female mouse ES cells KDM6A is specifically recruited to Rhox6 and 9 for gene activation, a process inhibited by Kdm6a knockdown. In contrast, KDM6A occupancy at Rhox6 and 9 is low in male ES cells and knockdown has no effect on expression. Our study implicates Kdm6a, a gene that escapes X inactivation, in the regulation of genes important in reproduction, suggesting that KDM6A may play a role in the etiology of developmental and reproduction-related effects of X chromosome anomalies.
2013-03-22 | GSE45390 | GEO
Project description:To address the functional role of MOF in mammalian X upregulation, male and female mouse ES cells were transfected with a mixture of three small interfering RNA duplexes, each of which targets a different region of Mof mRNA. We found that MOF knockdown in mouse ES cells caused a greater drop in expression of X-linked genes compared to autosomal genes, as measured by expression array analyses. The strongest effect was observed on medium-expressed X-linked genes. We next examined components of the two known MOF protein complexes, MSL1 (male-specific lethal1) and NSL1 (nonspecific lethal1). Knockdown of MSL1 but not NSL1 in undifferentiated female ES cells PGK12.1 specifically caused a decrease in expression levels of X-linked genes. Cells co-transfected with both MOF and MSL1 siRNAs had similar expression changes to MSL1 knockdown alone, indicating that these components probably operate within the same complex but are not additive. Our findings that key components of the MSL but not NSL complex play a role in upregulation of mammalian X-linked genes in ES cells. Mouse ES cells were treated by Invitrogen scramble siRNA duplexes or specific siRNA duplexes and used for RNA extraction and hybridization on Affymetrix microarrays. Six RNA samples from two independent double-RNAi treatments and one single-RNAi treatment in undifferentiated female ES cells PGK12.1, and RNA samples from two single-RNAi treatments in undifferentiated male ES cells WD44 or E14 were assayed for expression changes by arrays. RNA samples from three MSL1RNAi treatments, two MOF/MSL1RNAi treatments and three NSL1RNAi treatments in undifferentiated female ES cells PGK12.1 were assayed by arrays.
2013-02-15 | E-GEOD-44252 | biostudies-arrayexpress
Project description:To address the functional role of MOF in mammalian X upregulation, male and female mouse ES cells were transfected with a mixture of three small interfering RNA duplexes, each of which targets a different region of Mof mRNA. We found that MOF knockdown in mouse ES cells caused a greater drop in expression of X-linked genes compared to autosomal genes, as measured by expression array analyses. The strongest effect was observed on medium-expressed X-linked genes. We next examined components of the two known MOF protein complexes, MSL1 (male-specific lethal1) and NSL1 (nonspecific lethal1). Knockdown of MSL1 but not NSL1 in undifferentiated female ES cells PGK12.1 specifically caused a decrease in expression levels of X-linked genes. Cells co-transfected with both MOF and MSL1 siRNAs had similar expression changes to MSL1 knockdown alone, indicating that these components probably operate within the same complex but are not additive. Our findings that key components of the MSL but not NSL complex play a role in upregulation of mammalian X-linked genes in ES cells.
2013-02-15 | GSE44252 | GEO
Project description:KDM6A, which regulates gene expression by demethylation of the repressive histone mark H3K27me3, has a higher level in mammalian females than in males because the Kdm6a gene escapes X chromosome inactivation. Here, we report that maternal and paternal alleles of a number of genes throughout the genome are differentially regulated by KDM6A. Knockout of KDM6A in male and female embryonic stem cells derived from F1 hybrid mice results in downregulation of maternal alleles more frequently than paternal alleles. This parent-of-origin preference for regulation of gene expression by KDM6A was observed for subsets of maternally expressed non-imprinted and imprinted genes. By ATAC-seq downregulated genes showed a concomitant loss of chromatin accessibility on maternal but not on paternal alleles. Surprisingly, enrichment in H3K27me3 was observed on downregulated paternal but not maternal alleles. These results suggest parent-of-origin mechanisms of gene regulation by KDM6A, which may be histone demethylation-dependent and -independent.
2022-07-26 | GSE209788 | GEO
Project description:KDM6A, which regulates gene expression by demethylation of the repressive histone mark H3K27me3, has a higher level in mammalian females than in males because the Kdm6a gene escapes X chromosome inactivation. Here, we report that maternal and paternal alleles of a number of genes throughout the genome are differentially regulated by KDM6A. Knockout of KDM6A in male and female embryonic stem cells derived from F1 hybrid mice results in downregulation of maternal alleles more frequently than paternal alleles. This parent-of-origin preference for regulation of gene expression by KDM6A was observed for subsets of maternally expressed non-imprinted and imprinted genes. By ATAC-seq downregulated genes showed a concomitant loss of chromatin accessibility on maternal but not on paternal alleles. Surprisingly, enrichment in H3K27me3 was observed on downregulated paternal but not maternal alleles. These results suggest parent-of-origin mechanisms of gene regulation by KDM6A, which may be histone demethylation-dependent and -independent.
2022-07-26 | GSE209787 | GEO
Project description:KDM6A, which regulates gene expression by demethylation of the repressive histone mark H3K27me3, has a higher level in mammalian females than in males because the Kdm6a gene escapes X chromosome inactivation. Here, we report that maternal and paternal alleles of a number of genes throughout the genome are differentially regulated by KDM6A. Knockout of KDM6A in male and female embryonic stem cells derived from F1 hybrid mice results in downregulation of maternal alleles more frequently than paternal alleles. This parent-of-origin preference for regulation of gene expression by KDM6A was observed for subsets of maternally expressed non-imprinted and imprinted genes. By ATAC-seq downregulated genes showed a concomitant loss of chromatin accessibility on maternal but not on paternal alleles. Surprisingly, enrichment in H3K27me3 was observed on downregulated paternal but not maternal alleles. These results suggest parent-of-origin mechanisms of gene regulation by KDM6A, which may be histone demethylation-dependent and -independent.
2022-07-26 | GSE209786 | GEO
Project description:Paternal chromatin undergoes extensive structural and epigenetic changes during mammalian spermatogenesis, producing sperm with an epigenome optimized for the transition to embryogenesis. Lysine demethylase 6a (KDM6A, also called UTX) promotes gene activation in part via demethylation of H3K27me3, a developmentally important repressive modification abundant throughout the epigenome of spermatogenic cells and sperm. We previously demonstrated increased cancer risk in genetically wild type mice derived from a paternal germ line lacking Kdm6a (Kdm6a cKO), indicating a role for KDM6A in regulating heritable epigenetic states. However, the regulatory function of KDM6A during spermatogenesis is not known. Here, we show that Kdm6a is transiently expressed in spermatogenesis, with RNA and protein expression largely limited to late spermatogonia and early meiotic prophase. Kdm6a cKO males do not have defects in fertility or the overall progression of spermatogenesis. However, hundreds of genes are deregulated upon loss of Kdm6a in spermatogenic cells, with a strong bias towards downregulation coinciding with the time when Kdm6a is expressed. Misregulated genes encode factors involved in chromatin organization and regulation of repetitive elements, and a subset of these genes was persistently deregulated in the male germ line across two generations of offspring of Kdm6a cKO males. Genome-wide epigenetic profiling revealed broadening of H3K27me3 peaks in differentiating spermatogonia of Kdm6a cKO mice, suggesting that KDM6A demarcates H3K27me3 domains in the male germ line. Our findings highlight KDM6A as a transcriptional activator in the mammalian male germ line that is dispensable for spermatogenesis but important for safeguarding gene regulatory state intergenerationally.
2023-10-24 | GSE215112 | GEO
Project description:Transcriptional profile of murine Kdm6a null pancreatic cancer cell lines Loss-of-function mutations of KDM6A, an X chromosome encoded histone H3K27 demethylase, are frequent in a broad spectrum of epithelial and hematopoietic malignancies and contribute to oncogenesis with so far poorly characterized mechanisms. Pancreas specific ablation of Kdm6a in mice accelerated Kras-driven cell transformation and compromised survival in a gender specific manner. Female knockout animals were particularly vulnerable and developed aggressive squamous and quasi-mesenchymal tumors with metastatic potential, as opposed to males which developed adenocarcinomas and exhibited a better prognosis. Integration of gene expression studies coupled to ChIP-seq profiling of chromatin modifications demonstrated that loss of Kdm6a caused genome-wide remodeling of bivalent promoters and rewiring of enhancer chromatin to repress endodermal fate by activating c-MYC and TP63 dependent transcriptional programs favoring squamous and quasi-mesenchymal differentiation.
2018-04-01 | GSE98066 | GEO