ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR809/001/SRR8090371/SRR8090371_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR809/002/SRR8090372/SRR8090372_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR809/009/SRR8090369/SRR8090369_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR809/007/SRR8090367/SRR8090367_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR809/008/SRR8090368/SRR8090368_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR809/001/SRR8090371/SRR8090371_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR809/007/SRR8090367/SRR8090367_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR809/008/SRR8090368/SRR8090368_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR809/000/SRR8090370/SRR8090370_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR809/002/SRR8090372/SRR8090372_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR809/000/SRR8090370/SRR8090370_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR809/009/SRR8090369/SRR8090369_1.fastq.gzprimary200OKGenomicsLab LiFeng, medical genetics, Wuhan Universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA497996Homo sapiensWe 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. Overall design: We performed H3K9me3 ChIP-seq with wild-type (WT), shKDM4B and KDM4B in MCF7 cell linesxref:PubMed:30459150ENAfalseHistone demethylase KDM4B promotes DNA damage by activating long interspersed nuclear element-1Histone demethylase KDM4B promotes DNA damage by activating long interspersed nuclear element-12025-09-222018-10-25PRJNA497996GSE121642960630459150