Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genome-wide maps of KDM5 binding in drosophila adults

ABSTRACT: To determine which genes affected by loss of KDM5 in adults were direct targets, we carried out KDM5 ChIP-seq analyses. To valide this data, we utilized a previously generated fly strain in which the sole source of KDM5 is from a transgene expressing an HA tagged form of KDM5 expressed under the control of its endogenous promoter. Comparing genome-wide gene expression and KDM5 binding analyses in Drosophila adults, we demonstrate the primary function of KDM5 in adults is to activate gene expression KDM5. To investigate the link between KDM5 and H3K4me3, we carried out anti-H3K4me3 ChIP-seq from wildtype adults . Genome-wide, KDM5 and H3K4me3 peaks showed a similar distribution, with both peaking at the transcription start site (TSS) showed a striking overlap with the presence of H3K4me3. Examination of KDM5 binding and histone H3K4me3 modifications in drosophila adults

ORGANISM(S): Drosophila melanogaster

SUBMITTER: Julie Secombe

PROVIDER: E-GEOD-70589 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The Histone Demethylase KDM5 Activates Gene Expression by Recognizing Chromatin Context through Its PHD Reader Motif.

Liu Xingyin X Secombe Julie J

Cell reports 20151207 10

KDM5 family proteins are critically important transcriptional regulators whose physiological functions in the context of a whole animal remain largely unknown. Using genome-wide gene expression and binding analyses in Drosophila adults, we demonstrate that KDM5 (Lid) is a direct regulator of genes required for mitochondrial structure and function. Significantly, this occurs independently of KDM5's well-described JmjC domain-encoded histone demethylase activity. Instead, it requires the PHD motif ...[more]

PMID: 26673323

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Project description:Rationale: Human pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) provide a platform to identify and characterize factors that regulate the maturation of CMs. The transition from an immature fetal to adult CM state entails coordinated regulation of the expression of genes involved in myofibril formation and OXPHOS among others. Lysine demethylase 5 (KDM5) specifically demethylate H3K4me1/2/3 and have emerged as potential regulators of expression of genes involved in cardiac development and mitochondrial function.Objectives: The purpose of this study is to determine the role of KDM5 in iPSC-CM maturation.Methods and Results: KDM5A, B, and C proteins were mainly expressed in the early post-natal stages and their expressions were progressively downregulated in the postnatal cardiomyocytes and were absent in adult hearts and CMs. In contrast, KDM5 proteins were persistently expressed in the iPSC-CMs up to 60 days after the induction of myogenic differentiation, consistent with the immaturity of these cells. Inhibition of KDM5 by KDM5-C70 -a pan-KDM5 inhibitor, induced differential expression of 2,372 genes, including upregulation of genes involved in fatty acid oxidation (FAO), OXPHOS, and myogenesis in the iPSC-CMs. Likewise, genome-wide profiling of H3K4me3 binding sites by the CUT&RUN (Cleavage Under Targets & Release Using Nuclease) assay showed enriched of the H3K4me3 peaks at the promoter regions of genes encoding FAO, OXPHOS, and sarcomere proteins. Consistent with the chromatin and gene expression data, KDM5 inhibition increased expression of multiple sarcomere proteins and enhanced myofibrillar organization. Furthermore, inhibition of KDM5 increased H3K4me3 deposits at the promoter region of the ESRRA gene and increased its RNA and protein levels. Knockdown of ESRRA in KDM5-C70-treated iPSC-CM suppressed expression of a subset of the KDM5 targets. In conjunction with changes in the gene expression, KDM5 inhibition increased oxygen consumption rate and contractility in iPSC-CMs.

Dataset Information

Genome-wide maps of KDM5 binding in drosophila adults

Publications

The Histone Demethylase KDM5 Activates Gene Expression by Recognizing Chromatin Context through Its PHD Reader Motif.

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