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Status |
Public on Oct 24, 2018 |
Title |
Histone demethylase KDM4B promotes DNA damage by activating long interspersed nuclear element-1 |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
We assess whole-genome H3K9me3 distribution in cancer cells and find that H3K9me3 is largely enriched in long interspersed nuclear element-1 (LINE-1). A significant proportion of KDM4B-dependent H3K9me3 was located in evolutionarily young LINE-1 elements, which likely retain retrotransposition activity. Ectopic expression of KDM4B promoted LINE-1 expression, while depletion of KDM4B reduced it. Furthermore, KDM4B overexpression enhanced LINE-1 retrotransposition efficacy, copy number, and associated DNA damage, presumably via the histone demethylase activity of KDM4B. Breast cancer cell lines expressing high levels of KDM4B also exhibited increased LINE-1 expression and copy number compared with other cell lines. Pharmacological inhibition of KDM4B significantly reduced LINE-1 expression and DNA damage in breast cancer cells with excessive KDM4B. Our study not only identifies KDM4B as a novel regulator of LINE-1, but it also suggests an unexpected oncogenic role for KDM4B overexpression in tumorigenesis, providing clues for the development of new cancer prevention strategies and therapies.
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Overall design |
We performed H3K9me3 ChIP-seq with wild-type (WT), shKDM4B and KDM4B in MCF7 cell lines
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Contributor(s) |
Li F, Xiang Y |
Citation(s) |
30459150 |
Submission date |
Oct 23, 2018 |
Last update date |
Mar 20, 2019 |
Contact name |
Xiang Ying |
Organization name |
Wuhan University
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Department |
medical genetics
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Lab |
Lab LiFeng
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Street address |
Donghu road 185
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City |
Wuhan |
ZIP/Postal code |
430071 |
Country |
China |
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Platforms (1) |
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Samples (6)
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Relations |
BioProject |
PRJNA497996 |
SRA |
SRP166420 |
Supplementary file |
Size |
Download |
File type/resource |
GSE121642_RAW.tar |
1.5 Mb |
(http)(custom) |
TAR (of BED) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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