GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE141987 Query DataSets for GSE141987
Status Public on Mar 17, 2021
Title The dual function of JmjC domain-containing protein KDM5C in both gene transcriptional activation and repression promotes breast cancer cell growth and tumorigenesis [RNA-seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Emerging evidence suggested that epigenetic regulators can exhibit both co-activator and co-repressor activities in gene transcriptional regulation and disease development, such as cancer. However, how these dual activities are regulated and coordinated in cellular contexts remains elusive. Here, we reported that KDM5C, a repressive histone demethylase, is unexpectedly required for estrogen/estrogen receptor alpha (ERa)-induced gene transcriptional activation to promote cell proliferation, while it suppresses the expression of type I interferons (IFNs) and interferon-stimulated genes (ISGs) to escape from immuno-surveillance. KDM5C-interacting protein, ZMYND8, is found to be accompanied with KDM5C in regulation of both subsets of genes. Mechanistically, during estrogen/ERa-induced gene transcriptional activation, ERa interacts and recruits KDM5C/ZMYND8 to active enhancers, where ERa masks KDM5C’s demethylase activity towards H3K4me2/3, converting KDM5C from a co-repressor to a co-activator. Furthermore, KDM5C and ZMYND8 are found to recruit the P-TEFb complex in a cooperative manner to activate estrogen/ERa-target genes. In contrast, KDM5C/ZMYND8 represses type I IFNs and ISGs through directly interfering TBK1 phosphorylation in an enzymatic-dependent manner. The combinatory effects of KDM5C’s dual activities in regulation of genes involved in both cell proliferation and immuno-escape lead to breast cancer cell proliferation in vitro and xenograft growth in mice. Taken together, we revealed a mechanism by which a repressive epigenetic regulator can be converted to a co-activator under specific signal cues to regulate specific gene programs, and the dual nature as both a co-repressor and co-activator together contributes to cancer development.
Overall design RNA-seq performed in this study was designed to understand the molecular mechanisms underlying KDM5C in gene transcription regulation.
Web link
Contributor(s) Liu W, Shen H, Zhang W, Hu G
Citation(s) 33977073
Submission date Dec 13, 2019
Last update date May 19, 2021
Contact name Guosheng Hu
Phone 15506972603
Organization name xiamen University
Department School of Pharmaceutical Sciences
Lab liulab
Street address Xiang'an South Road, Xiang'an District
City Xiamen
State/province Fujian
ZIP/Postal code 361102
Country China
Platforms (2)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (8)
GSM4217414 RNA-Seq-siCTL-CTL-MCF-7-rep1
GSM4217415 RNA-Seq-siCTL-E2-MCF-7-rep1
GSM4217416 RNA-Seq-siKDM5C-CTL-MCF-7-rep1
This SubSeries is part of SuperSeries:
GSE141988 The dual function of JmjC domain-containing protein KDM5C in both gene transcriptional activation and repression promotes breast cancer cell growth and tumorigenesis
BioProject PRJNA595509
SRA SRP237512

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE141987_RAW.tar 905.6 Mb (http)(custom) TAR (of BIGWIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap