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KDM5A epigenetically orchestrates MHC-I associated anti-tumor immunity of immunotherapy

ABSTRACT: KDM5A epigenetically orchestrates MHC-I associated anti-tumor immunity of immunotherapy

PROVIDER: PRJNA1077950 | ENA |

REPOSITORIES: ENA

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KDM5A epigenetically orchestrates MHC-I associated anti-tumor immunity of immunotherapy [DC RNA-seq]

Project description:Immune checkpoint blockade (ICB) therapy revolutionized cancer treatment, but many patients with impaired MHC-I expression remain refractory. Histone methylation was involved in anti-tumor immunity of ICB. However, the link between histone methylation and MHC-I regulation and the related mechanisms are poorly understood. Here we show that KDM5A, an H3K4 demethylase that is critical for MHC-I expression and associated antigen presentation capacity, induces robust immune response and enhances ICB efficacy. Mechanistically, KDM5A upregulates IFN-gamma/STAT1-mediated MHC-I expression via directly binding and suppressing Scos1 in tumor cells. The genes encoding the lysosomal cathepsins are recognized and up-regulated by KDM5A, resulting in enhanced antigen-presentation abilities of both tumor cells and dendritic cells. Furthermore, pharmacological enhancing KDM5A improves response to anti-PD-1 therapy. These investigations demonstrate that enhancing KDM5A triggers MHC-associated antigen presentation of both tumor cells and DCs simultaneously to boost antitumor immunity, thus represents a candidate ICB sensitizer.

2024-03-31 | GSE260912 | GEO

Project description:KDM5A epigenetically orchestrates MHC-I associated anti-tumor immunity of immunotherapy

| PRJNA1077463 | ENA

KDM5A epigenetically orchestrates MHC-I associated anti-tumor immunity of immunotherapy

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

2024-03-31 | GSE256057 | GEO

Gene expression profiles of KDM5A-/- MEFs with wild-type KDM5A or KDM5A-H483A mutant

Project description:Gene expression profiles of Immortalized KDM5A-/- MEFs with re-introduction of wild-type KDM5A or KDM5A-H483A mutant.

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Genome-wide maps of KDM5A/JARID1A/RBP2 in mouse ES cells.

Project description:We report the identification of genomic regions bound by KDM5A in mouse embryonic stem (ES) cells and define the functional categories that these regions represent. KDM5A modifies methylated lysine residues on histone tails. We developed anti-KDM5A antibodies and set to detect genomic regions enriched with these antibodies using cells with normal Kdm5a or cells from Kdm5a knockout mice as a control. We found high enrichment with the KDM5A antibodies in normal cells when compared with the genomic background. We found striking identity in the regions enriched with these antibodies in normal cells when compared with the total genomic DNA or with KDM5A ChIP assays from Kdm5a KO cells, showing that the antibodies are specific. Examination of target genes in ES cells

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Genome-wide KDM5A occupancy after MK2206/DMSO treatment of T47D cells

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2016-06-14 | E-GEOD-80593 | biostudies-arrayexpress

Myogeneic differentiation in Rb1 or Kdm5a/Jarid1a/Rbp2 deficient mouse embryonic fibroblasts.

Project description:Cells lacking Rb1 are deficient in differentiation. Loss of Kdm5a rescues myogenic differentiation, as judged by appearance of morphologically normal myotubes that display expression of late markers of differentiation. In order to better understand how Kdm5a loss rescues differentiation, we induced mouse embryonic fibroblasts (MEFs) of different genotypes to undergo myogenic differentiation and analyzed gene expression changes in wild-type, Kdm5a-/-, Rb1-/- and Kdm5a-/-; Rb1-/- cells. Rb1-/- cells stained single nucleated, did not exhibit morphological changes and increased expression of the myogenic marker MYHC. Except for Rb1-/- cells, all other cells were undergoing successful convertion into aligned multinucleated myotubes and were MYHC-positive. We obtained purified populations of myotubes for the wild-type and Kdm5a-/-; Rb1-/- cells. RNA-seq analysis of gene expression in Rb1 or Kdm5a deficient MEFs that were induced for myogenic differentiation.

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KDM5A regulates p53 function

Project description:KDM5A regulates p53 function

| PRJNA419354 | ENA

Genome-wide maps of KDM5A/JARID1A/RBP2 in mouse ES cells.

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KDM5A regulates p53 function

Project description:KDM5A regulates p53 expression by modulating the expression of a subgroup of translation iniation genes.

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