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Deficiency of histone methyltransferase SETD2 in liver leads to abnormal lipid metabolism and hepatocarcinoma [ChIP-Seq]

ABSTRACT: Deficiency of histone methyltransferase SETD2 in liver leads to abnormal lipid metabolism and hepatocarcinoma [ChIP-Seq]

PROVIDER: PRJNA563561 | ENA |

REPOSITORIES: ENA

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Deficiency of histone methyltransferase SETD2 in liver leads to abnormal lipid metabolism and hepatocarcinoma [ChIP-Seq]

Project description:H3K36me3 catalyzed by histone methyltransferase SETD2 is one of the most conserved epigenetic marks from yeast to mammals. SETD2 is frequently mutated in multiple cancers and acts as a tumor suppressor. Here, utilizing a liver-specific deletion of Setd2 mice model, we found that Setd2 depletion is sufficient to trigger hepatocarcinoma (HCC) spontaneously. Meanwhile, in a DEN-induced HCC model, Setd2 depletion significantly promoted tumor number and size. The mechanistic study showed that Setd2 suppresses HCC not only through modulating DNA damage response, but also regulating lipid metabolism in liver. Setd2 deficiency down-regulated the expression of cholesterol efflux genes and caused lipid accumulation. ChIP-Seq analysis further revealed that Setd2 deletion induced AP-1 activation in liver, which was probably trigged by accumulated cholesterol. AP-1 is a well-known oncogene in HCC and inhibits p53 in Setd2-deficient cells. Taken together, we found the role of an important epigenetic gene in regulating cholesterol homeostasis and HCC, and revealed the underlying mechanisms.

2021-09-01 | GSE136743 | GEO

Deficiency of histone methyltransferase SETD2 in liver leads to abnormal lipid metabolism and hepatocarcinoma [RNA-Seq]

2021-09-01 | GSE136742 | GEO

Deficiency of histone methyltransferase SETD2 in liver leads to abnormal lipid metabolism and hepatocarcinoma

Project description:Deficiency of histone methyltransferase SETD2 in liver leads to abnormal lipid metabolism and hepatocarcinoma

| PRJNA563558 | ENA

Deficiency of histone methyltransferase SETD2 in liver leads to abnormal lipid metabolism and hepatocarcinoma [RNA-Seq]

Project description:Deficiency of histone methyltransferase SETD2 in liver leads to abnormal lipid metabolism and hepatocarcinoma [RNA-Seq]

| PRJNA563560 | ENA

Deficiency of histone methyltransferase SETD2 in liver leads to abnormal lipid metabolism and hepatocarcinoma

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

2021-09-01 | GSE136744 | GEO

Abnormal neocortex arealization and Sotos-like syndrome-associated behavior in Setd2 mutant mice

Project description:Epigenetic regulation of gene expression through histone modifications like methylation of various lysine residues are essential for embryonic development. Here we removed SETD2, a methyltransferase for histone 3 lysine 36 trimethylation (H3K36me3), in the developing dorsal forebrain in mice and show it is required for proper area patterning (arealization) of the neocortex and the formation of thalamo-cortico-thalamic circuits by maintaining the expression of clustered protocadherin (Pcdh) genes in an H3K36me3 methyltransferase-dependent manner. Moreover, the Setd2 mutant mice exhibit defects in social interaction, motor endurance and spatial memory, reminiscent of patients with the Sotos-like syndrome bearing SETD2 mutations.

2020-10-01 | GSE138153 | GEO

Abnormal neocortex arealization and Sotos-like syndrome-associated behavior in Setd2 mutant mice

2020-09-30 | GSE137622 | GEO

The methyltransferase activity of Setd2 is essential for mouse embryonic development: establishment of a mouse model harboring a patient-derived Setd2 mutation

Project description:The histone methyltransferase SETD2 is responsible for the transcription-coupled trimethylation of histone H3 lysine 36 (H3K36me3) on all protein-coding genes through its direct interaction with the elongating form of RNA polymerase II. In mice, Setd2 is required for embryonic development, as the Setd2-null mice are embryonic lethal due to impaired vascular remodeling. In human, SETD2 is frequently mutated in various types of cancer, thus representing one of the major chromatin-modification defects that drive tumorigenesis. Notably, recent studies suggest that, despite the central roles of their catalytic activities, many chromatin modifiers contain important non-catalytic (so-called “moonlighting”) functions, which are largely substantiated by their roles in protein-protein interactions. This notion is somewhat consistent with the observation that the cancer-associated SETD2 mutations are seemingly localized throughout the whole protein, thus raising a question whether the major function(s) of SETD2 is solely dependent on its methyltransferase activity. As an answer to this question, in this short report, we have established a site-specific Setd2 knock-in mouse model harboring a patient-derived, catalytic dead Setd2 and have provided clear evidence supporting that the requirement of Setd2 in mouse embryonic development is definitely dependent on its methyltransferase activity. However, it is also notable that, in comparison with the Setd2-null mice, the Setd2 catalytic dead mice showed slightly mild defects in embryonic development and gene expression changes, suggesting potential non-catalytic functions of Setd2, which could be studied in the future by using these different Setd2 mouse models.

2024-01-01 | GSE241154 | GEO

The histone methyltransferase SETD2 couples transcription and splicing by engaging pre-mRNA processing factors through its SHI domain

Project description:The domains of SETD2, a known histone methyltransferase were investigated for specific interaction partners and function using a number of biochemical assays and affinity purification mass spectrometry. The C-terminal domain, named SETD2C, was identified to interact with hnRNP-L through a previously uncharacterized domain. These findings demonstrate the crosstalk between the transcription and splicing machinery.

2021-02-01 | PXD019538 | Pride

The histone methyltransferase SETD2 couples transcription and splicing by engaging pre-mRNA processing factors through its SHI domain

2021-02-01 | PXD019376 | Pride

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