Project description:We discovered that the Saccharomyces cerevisiae lysine demethylase, Jhd2 (also known as KDM5), recruits 3'UTR processing machinery and promotes alteration of 3'UTR length in a demethylase-dependent manner. Interaction of Jhd2 with both chromatin and RNA suggests that Jhd2 affects selection of polyadenylation sites through a transcription-coupled mechanism. For 3'READs analysis, wild-type yeast or yeast with JHD2 deleted were grown to mid-log phase and RNA was extracted as mentioned above. cDNA libraries enriched for 3'UTRs were prepared as previously published and as noted in Figure 4a [28]. Samples were then subjected to RNA sequencing on the Illumina Hiseq 2000 using 50bp single end reads. Data was analyzed as previously [Hoque M] with the following modifications: The adapter sequences were trimmed off the single-ended reads. The remaining reads longer than 15 bp were mapped to yeast genome SacCer3 using bowtie2 [Langmead B 2012] with the setting '-5 4 --local', trimming off 4bp from 5' and allowing soft clipping (S) at both ends. The alignments were then filtered by 1) MAPQ>=10, 2) mismatches <= 5%, 3) unaligned 5' Ts >=2 to get the PASS reads. The last aligned positions of the PASS reads were grouped to pA clusters with a clustering size of 24 bp. Each pA cluster was assigned to one of the genes defined by SGD [Cherry JM]. The 3' end of a gene was extended 1000bp from the end of CDS until it overlaps with another gene in the same direction. The pA Clusters were then filtered by contains 1) >= 3 PASS reads 2) >= 5% of all PASS reads mapped to the gene.

2016-03-23 | E-GEOD-67163 | biostudies-arrayexpress

KDM5 lysine demethylases are involved in maintenance of 3'UTR length.

Project description:The complexity by which cells regulate gene and protein expression is multifaceted and intricate. Regulation of 3' untranslated region (UTR) processing of mRNA has been shown to play a critical role in development and disease. However, the process by which cells select alternative mRNA forms is not well understood. We discovered that the Saccharomyces cerevisiae lysine demethylase, Jhd2 (also known as KDM5), recruits 3'UTR processing machinery and promotes alteration of 3'UTR length for some genes in a demethylase-dependent manner. Interaction of Jhd2 with both chromatin and RNA suggests that Jhd2 affects selection of polyadenylation sites through a transcription-coupled mechanism. Furthermore, its mammalian homolog KDM5B (also known as JARID1B or PLU1), but not KDM5A (also known as JARID1A or RBP2), promotes shortening of CCND1 transcript in breast cancer cells. Consistent with these results, KDM5B expression correlates with shortened CCND1 in human breast tumor tissues. In contrast, both KDM5A and KDM5B are involved in the lengthening of DICER1. Our findings suggest both a novel role for this family of demethylases and a novel targetable mechanism for 3'UTR processing.

| S-EPMC5262454 | biostudies-literature

KDM5 Lysine Demethylases Are Involved in Maintenance of 3'UTR Length

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-03-23 | E-GEOD-67212 | biostudies-arrayexpress

KDM5 histone demethylases repress innate immune response via suppression of STING

Project description:Tri-methylation on histone H3 lysine 4 (H3K4me3) is enriched near transcription start sites and correlates with active transcription. Like other histone marks, methylation on H3K4 is catalyzed by the respective methyltransferases and erased by demethylases. Lysine demethylase 5 (KDM5) family of Fe (II) and α-ketoglutarate-dependent dioxygenases removes the methyl groups from H3K4me3. All four family members of KDM5 demethylases (KDM5A-D) share sequence identity, have similar in vitro kinetic parameters, and display functional redundancy. To determine the effects of complete depletion of KDM5 activity, we treated MCF7 cells with DMSO, or two pan-KDM5 specific inhibitors, KDM5-C70 (our lab code 443) and CPI-48 (our lab code 278) and performed RNA sequencing to determine gene expression changes after KDM5 inhibitor treatment.

2018-07-03 | GSE108502 | GEO

KDM5 Lysine Demethylases Are Involved in Maintenance of 3'UTR Length

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-03-23 | GSE67212 | GEO

(R)-2-hydroxyglutarate inhibits KDM5 histone lysine demethylases to drive tumorigenesis in IDH-mutant cancers

Project description:Oncogenic mutations in isocitrate dehydrogenase (IDH)-1 and -2 occur in a wide range of cancers, including acute myeloid leukemias (AMLs) and gliomas1-3. Mutant IDH enzymes convert 2-oxoglutarate (2OG) to (R)-2-hydroxyglutarate [(R)-2HG]4,5, an oncometabolite that induces cellular transformation by dysregulating 2OG-dependent enzymes. The only direct target of (R)-2HG known to contribute to transformation is the 5-methylcytosine hydroxylase TET2, and there is ample evidence to suggest that (R)-2HG drives leukemogenesis at least in part by inhibiting TET26,7. However, IDH mutations, but not TET2 mutations, are specifically associated with aggressive hematologic diseases, suggesting that (R)-2HG has targets other than TET2 that contribute to mutant IDH-mediated transformation. Here, we report that (R)-2HG directly inhibits KDM5 histone lysine demethylases in IDH-mutant AMLs and gliomas to induce cellular transformation. These studies provide a functional link between dysregulation of histone lysine methylation and tumorigenesis in IDH-mutant cancers.

2023-03-01 | GSE184611 | GEO

(R)-2-hydroxyglutarate inhibits KDM5 histone lysine demethylases to drive tumorigenesis in IDH-mutant cancers

Project description:(R)-2-hydroxyglutarate inhibits KDM5 histone lysine demethylases to drive tumorigenesis in IDH-mutant cancers

| PRJNA765357 | ENA