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Omics · study · 2026

KDM5C and KDM5D influence DNA methylation in adult mouse liver

Listed in NCBI GEO

Background.

Description

Several lines of evidence suggest that the sex-chromosome complement influences autosomal gene regulation and DNA methylation, however, the exact molecular mechanisms responsible for such effects remain elusive. X-linked epigenetic modifiers that escape X-chromosome inactivation, and hence have higher dosage in female cells, are the primary gene candidates for mediating the effects of X-dosage, whereas Y-linked paralogs may rescue such imbalance or have distinct effects on methylation.

Methods. Here, we tested the impacts of mutations in mouse histone lysine 4 demethylases Kdm5c (X-linked) and Kdm5d (Y-linked) on DNA methylation in mouse liver. KDM5C and KDM5D demethylate H3K4me2/3 thereby facilitating DNA methylation of their target DNA regions.

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Therefore, loss of either Kdm5c or Kdm5d is expected to reduce DNA methylation at such regions. We hypothesized that Kdm5c gene dosage was responsible for the X-dosage dependent DNA methylation in mouse liver and compared DNA methylation patterns in heterozygous mutant Kdm5c+/- and wild type females using whole genome bisulfite sequencing (WGBS) and DSS. Results.

We examined the impacts of mutations in Kdm5c or Kdm5d on genome-wide DNA methylation and found that they had different targets but tended to map close to H3K4me1-enriched regions. We also compared the Kdm5c and Kdm5d sensitive regions to regions with sex-chromosome complement dependent DNA methylation and found no overlaps. Conclusions.

In summary, while Kdm5c and Kdm5d have multi-locus effects on DNA methylation in mouse liver, they are unlikely to be solely responsible for sex-chromosome complement effects on DNA methylation in adult mouse liver.

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From keywords
Life Sciences
Inferred from text
Sequencing 75%
Provenance · 1 source records, 8 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE30721113 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:methylation-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[modality].local:modality:sequencingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[organism].NCBITaxon:10090source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title