Similar Datasets
Project description:JMJD6 expression was shown to have different roles in estrogen receptor (ER)-positive and -negative breast cancer cells
2023-01-01 | GSE216234 | GEO
Project description:Enhancers are genomic regulatory elements shown to play key roles in controlling cell type-specific gene expression, regulated by signal-dependent transcription factors and co-factors. Distinct classes of enhancers can specify distinct gene expression profiles and biological outcomes. Recent studies suggested that bidirectional non-coding RNAs (ncRNAs), referred as enhancer RNA (eRNAs), are transcribed on enhancers, which are tightly associated with enhancer activity. However, the protein factors which govern the activation of enhancers remain poorly characterized. Here we reported that a Jumonji C (JmjC) domain-containing protein demethylase, JMJD6, is a determinant for estrogen/estrogen receptor (ER)-induced enhancer activation, coding gene transcription, breast cancer cell growth and tumorigenesis. Mechanistically, JMJD6 was found to be specifically recruited onto ER-bound active enhancers in response to estrogen stimulation, which was required for RNA Pol II recruitment and eRNA production of enhancers, leading to transcriptional activation of cognate estrogen target genes. Furthermore, JMJD6 was found to be physically and functionally associated with MED12 in the mediator complex to regulate estrogen-induced transcriptional activation, with JMJD6 was required for MED12 recruitment onto active enhancers. Specifically, JMJD6 was essential for MED12 to interact with CARM1, an arginine methyltransferase well known to be implicated in estrogen-induced transcriptional activation, which methylated MED12 at its c-terminus at multiple arginine methylation sites and was required for MED12 binding with chromatin. Collectively, our data uncovered a critical regulator of estrogen/estrogen receptor-induced enhancer activation and coding gene transcription, providing a potential drug candidate for developing novel strategies targeting ER-positive breast cancers.
2018-04-16 | GSE101560 | GEO
Project description:Enhancers are genomic regulatory elements shown to play key roles in controlling cell type-specific gene expression, regulated by signal-dependent transcription factors and co-factors. Distinct classes of enhancers can specify distinct gene expression profiles and biological outcomes. Recent studies suggested that bidirectional non-coding RNAs (ncRNAs), referred as enhancer RNA (eRNAs), are transcribed on enhancers, which are tightly associated with enhancer activity. However, the protein factors which govern the activation of enhancers remain poorly characterized. Here we reported that a Jumonji C (JmjC) domain-containing protein demethylase, JMJD6, is a determinant for estrogen/estrogen receptor (ER)-induced enhancer activation, coding gene transcription, breast cancer cell growth and tumorigenesis. Mechanistically, JMJD6 was found to be specifically recruited onto ER-bound active enhancers in response to estrogen stimulation, which was required for RNA Pol II recruitment and eRNA production of enhancers, leading to transcriptional activation of cognate estrogen target genes. Furthermore, JMJD6 was found to be physically and functionally associated with MED12 in the mediator complex to regulate estrogen-induced transcriptional activation, with JMJD6 was required for MED12 recruitment onto active enhancers. Specifically, JMJD6 was essential for MED12 to interact with CARM1, an arginine methyltransferase well known to be implicated in estrogen-induced transcriptional activation, which methylated MED12 at its c-terminus at multiple arginine methylation sites and was required for MED12 binding with chromatin. Collectively, our data uncovered a critical regulator of estrogen/estrogen receptor-induced enhancer activation and coding gene transcription, providing a potential drug candidate for developing novel strategies targeting ER-positive breast cancers.
2018-04-16 | GSE101559 | GEO
Project description:To investigate the function of tyrosyl-DNA phosphodiesterase 2 (TDP2) in estrogen receptor (ER) positive breast cancer, we perfomed bulk and single-cell RNA-seq on MCF7 and MCF7 TDP2-KO cells treated with/without estrogen .
2024-04-17 | GSE225423 | GEO
Project description:By survival analysis of breast cancer patients, JMJD6 was found to be significantly associated with poor prognosis. Over-expression and knock-down of JMJD6 in breast cancer cell lines suggested a role in proliferation. In order to study the transcriptional events that occur following JMJD6 expression changes, siRNA-mediated knock-down of JMJD6 was performed in MCF-7 and MDA-MB231 and stable over-expression of JMJD6 was performed in MCF-7. There are 2 different siRNA-mediated knock-downs of JMJD6 with 2 biological replicates in MCF-7 and MDA-MB231; 3 clones of JMJD6 over-expression with 3 biological replicates in MCF-7. The control for the knock-downs is scrambled siRNA-treated MCF-7 and MDA-MB231 and the control for JMJD6 over-expression is empty vector over-expression in MCF-7.
2012-05-09 | E-GEOD-31782 | biostudies-arrayexpress
Project description:In our study we showed that JMJD6 expression in tumor cells can regulate macrophage differentiation in vitro through ANXA-1 secretion. For this experiment we cultured RAW264.7 cells cultured in conditioned medium of SCR or JMJD6-KO breast cancer PymT-41C cells for 24hrs and we then submitted the RAW264.7 cells for ClariomD assay
2022-01-03 | GSE164399 | GEO
Project description:By survival analysis of breast cancer patients, JMJD6 was found to be significantly associated with poor prognosis. Over-expression and knock-down of JMJD6 in breast cancer cell lines suggested a role in proliferation. In order to study the transcriptional events that occur following JMJD6 expression changes, siRNA-mediated knock-down of JMJD6 was performed in MCF-7 and MDA-MB231 and stable over-expression of JMJD6 was performed in MCF-7.
2012-05-10 | GSE31782 | GEO
Project description:The expression levels of JMJD6 and its correlation with H2A.XY39ph differed in TNBC and non-TNBC cells. In addition, we have previously shown that H2A.XY39ph levels are positively correlated with tumor size, histological grade and advanced TNM stage in breast cancer. To analyze the role of JMJD6 in regulating the characteristics of different subtypes of breast cancer, the transcriptomes of TNBC cells (SUM159) and non-TNBC cells (HCC1569) that overexpressed JMJD6 were compared. We speculate that JMJD6 overexpression cause autophagy pathway activation in TNBC via enhancing ATG genes expression.
2023-10-01 | E-MTAB-6517 | biostudies-arrayexpress
Project description:To investigate molecular mechanisms of resistance, we used two different in vivo xenograft models of estrogen receptor-positive (ER+) breast cancer, with or without HER2 over-expression (MCF7/HER2-18 and MCF7 wt, respectively). Mice with established tumors were assigned to the following treatment groups: continued estrogen supplementation (E2), estrogen deprivation (ED), ED plus tamoxifen (Tam), all with or without the EGFR tyrosine kinase inhibitor gefinitinib (G). Another group received ED plus the antiestrogen fulvestrant (MCF7 wt only). Tumors with acquired or de novo resistance to these endocrine therapies were profiled for mRNA expression using Affymetrix Genechip arrays. This SuperSeries is composed of the SubSeries listed below.
2008-12-01 | GSE8141 | GEO
Project description:The Jumonji domaining-containing protein JMJD6 is a 2-oxoglutarate dependent dioxygenase that has been implicated in a broad range of biological functions. Cellular studies have implicated the enzyme in chromatin biology, transcription, DNA repair, mRNA splicing and co-transcriptional processing. Although not all studies agree, JMJD6 has been reported to catalyse both hydroxylation of lysine residues and demethylation of arginine residues. However, despite extensive study and the indirect implication of JMJD6 catalysis in many cellular processes, direct assignment of JMJD6 catalytic substrates has been limited. Examination of a site of reported prolyl hydroxylation within a lysine-rich region of the bromodomain protein BRD4 led us to conclude that hydroxylation was in fact on lysine and catalysed by Jmjd6. This prompted a wider search for JMJD6-catalysed protein modifications deploying mass spectrometric methods designed to identify novel substrate associations and facilitate analysis of lysine-rich regions by LC-MSMS. Using derivatization of lysine with propionic anhydride to improve the analysis of tryptic peptides and a pharmacological inhibitor of JMJD6 to stabilise enzyme/substrate associations, we report over 100 sites of JMJD6-catalysed lysyl hydroxylation on 48 protein substrates including 19 sites of hydroxylation on BRD4. Most hydroxylations were within lysine-rich regions that are predicted to be unstructured; in some multiple modifications were observed on adjacent lysine residues. Almost all of the JMJD6 substrates defined in this study have been associated with membraneless organelle formation. Taken together with findings implicating lysine-rich regions in subcellular partitioning by liquid-liquid phase separation, our findings raise the possibility that JMJD6 may play a role in regulating such processes in response to stresses, including hypoxia. Note, this dataset corresponds to Figure 3 of the published manuscript; which employs a substrate-trapping methodology to identify novel substrates of JMJD6 by label free DIA approach.
2022-08-02 | PXD031155 | Pride