Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Sex-biased and parental allele-specific gene regulation by KDM6A

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus musculus x Mus musculus castaneus

PROVIDER: GSE209789 | GEO | 2022/07/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Sex-biased and parental allele-specific gene regulation by KDM6A.

Project description:BackgroundKDM6A is a demethylase encoded by a gene with female-biased expression due to escape from X inactivation. Its main role is to facilitate gene expression through removal of the repressive H3K27me3 mark, with evidence of some additional histone demethylase-independent functions. KDM6A mutations have been implicated in congenital disorders such as Kabuki Syndrome, as well as in sex differences in cancer.MethodsKdm6a was knocked out using CRISPR/Cas9 gene editing in F1 male and female mouse embryonic stem cells (ES) derived from reciprocal crosses between C57BL6 x Mus castaneus. Diploid and allelic RNA-seq analyses were done to compare gene expression between wild-type and Kdm6a knockout (KO) clones. The effects of Kdm6a KO on sex-biased gene expression were investigated by comparing gene expression between male and female ES cells. Changes in H3K27me3 enrichment and chromatin accessibility at promoter regions of genes with expression changes were characterized by ChIP-seq and ATAC-seq followed by diploid and allelic analyses.ResultsWe report that Kdm6a KO in male and female embryonic stem (ES) cells derived from F1 hybrid mice cause extensive gene dysregulation, disruption of sex biases, and specific parental allele effects. Among the dysregulated genes are candidate genes that may explain abnormal developmental features of Kabuki syndrome caused by KDM6A mutations in human. Strikingly, Kdm6a knockouts result in a decrease in sex-biased expression and in preferential downregulation of the maternal alleles of a number of genes. Most promoters of dysregulated genes show concordant epigenetic changes including gain of H3K27me3 and loss of chromatin accessibility, but there was less concordance when considering allelic changes.ConclusionsOur study reveals new sex-related roles of KDM6A in the regulation of developmental genes, the maintenance of sex-biased gene expression, and the differential expression of parental alleles.

| S-EPMC9308343 | biostudies-literature

Sex-biased and parental allele-specific gene regulation by KDM6A [RNA-seq]

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

Sex-biased and parental allele-specific gene regulation by KDM6A [ChIP-seq]

2022-07-26 | GSE209787 | GEO

Sex-biased and parental allele-specific gene regulation by KDM6A [ATAC-seq]

2022-07-26 | GSE209786 | GEO

Sex-biased and parental allele-specific gene regulation by KDM6A

Project description:Sex-biased and parental allele-specific gene regulation by KDM6A

| PRJNA862468 | ENA

Sex-biased and parental allele-specific gene regulation by KDM6A [ChIP-seq]

Project description:Sex-biased and parental allele-specific gene regulation by KDM6A [ChIP-seq]

| PRJNA862470 | ENA

Sex-biased and parental allele-specific gene regulation by KDM6A [ATAC-seq]