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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Bound chromatin analysis of mouse Zfp92 in MIN6 cells

ABSTRACT: Zfp92, a repressive KRAB domain-containing zinc-finger protein, was identified by Gene Co-expression Network analysis to be an interesting candidate gene involved in endocrine specification and maturation. We examined the role of Zfp92, a KRAB-ZFP that is highly expressed in pancreatic islets of adult mice, by analyzing global Zfp92 knockout (KO) mice. Adult Zfp92 KO animals exhibited only mild changes in glucose homeostasis and no change in islet structure, although, male KO mice exhibited decreased growth, and female KO mice exhibited increased body fat accumulation on a high fat diet. We found that Zfp92 regulates a subset of transposable elements as well as Mafb, a transcription factor involved in islet development.

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Mus musculus

SUBMITTER: Anna Osipovich

PROVIDER: E-MTAB-12576 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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RNA-Seq analysis of mouse Zfp92 knockout vs wild-type adult pancreatic islets

Project description:Zfp92, a repressive KRAB domain-containing zinc-finger protein, was identified by Gene Co-expression Network analysis to be an interesting candidate gene involved in endocrine specification and maturation. We examined the role of Zfp92, a KRAB-ZFP that is highly expressed in pancreatic islets of adult mice, by analyzing global Zfp92 knockout (KO) mice. Adult Zfp92 KO animals exhibited only mild changes in glucose homeostasis and no change in islet structure, although, male KO mice exhibited decreased growth, and female KO mice exhibited increased body fat accumulation on a high fat diet. We found that Zfp92 regulates a subset of transposable elements as well as Mafb, a transcription factor involved in islet development.

2022-12-02 | E-MTAB-11637 | biostudies-arrayexpress

Transposable elements and their KRAB-ZFP controllers regulate gene expression in adult tissues

Project description:The tetrapod-restricted KRAB-containing zinc finger proteins (KRAB-ZFPs) are essential early embryonic controllers of transposable elements (TEs), which they repress via their cofactor KAP1 and associated effectors through histone and DNA methylation, a process thought to result in irreversible silencing. Using a target-centered functional screen, we matched several murine TEs with their cognate KRAB-ZFP. This revealed an unexpected level of granularity in their interactions, with KRAB-ZFPs recognizing TEs from more than one subfamily, TEs recruiting more than one KRAB-ZFP, and spatially and temporally differential KRAB-ZFP-mediated regulation of TEs and nearby genes. Most importantly, we discovered that the KRAB/KAP1 system controls TEs in adult tissues, in cell culture and in vivo, where they partner up to regulate the expression of cellular genes. Therefore, TEs and KRAB-ZFPs establish widely active transcription networks that regulate not only development but probably also many physiological events. Given the high degree of species-specificity of both TEs and KRAB-ZFPs, these results have important implications for studying and understanding the biology of higher vertebrates, including humans. Analysis of transcriptional profiles of KAP1 or ZFP932/Gm15446 KO cells or tissues, and ZFP932 and Gm15446 ChIPseq in murine ES and C2C12 cells.

2016-03-15 | E-GEOD-74278 | biostudies-arrayexpress

KRAB Zincfinger Interactome - The interactome of KRAB zinc finger proteins reveals the evolutionary history of their functional diversification

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2019-06-04 | PXD011322 | Pride

Effect of LINC00899 depletion on histone mark enrichment in HeLa cells

Project description:LncRNAs represent a major transcriptional output of the human genome, but the function of many of these elements is unknown. In this experiment, we have used the ‘CUT&RUN’ technique to quantify the changes in histone mark enrichment across the genome upon depletion of the lncRNA LINC00899 in HeLa cells. LINC00899 is of interest as its depletion results in mitotic delay, suggesting a role in mitotic progression. The CUT&RUN procedure uses antibodies to target a nuclease to the relevant protein binding site, cleaving the surrounding DNA for sequencing and yielding output equivalent to that of ChIP-seq. This experiment contains 2 replicate batches where each batch contains a sample with LINC00899 knocked down by RNA interference (RNAi); a RNAi negative control; a sample with LINC00899 knocked down with locked nucleic acid antisense oligonucleotides (LNA); and a LNA negative control. This was performed using antibodies against H3K4me3, H3K27ac, H3K36me3 and H3K27me3, as well as an IgG (goat-derived anti-rabbit) control. All samples in each batch were generated at the same time. Within each batch, all CUT&RUN experiments with the same knockdown were performed on nuclei obtained from the same cell culture. Independent cell cultures were used for experiments with different knockdown or in different batches.

2019-03-29 | E-MTAB-7419 | biostudies-arrayexpress

Evollutionally dynamic L1 regulation in embryonic stem cells

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2014-06-09 | E-GEOD-58323 | biostudies-arrayexpress

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ChIP-seq analysis of KAP1 and H3K9me3 modifications in mouse spleen B cells

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Enhanced Pathogenicity of Th17 cells Generated in the Absence of Transforming Growth Factor-β Signaling

Project description:CD4+ T cells that selectively produce interleukin (IL)-17, are critical for host defense and autoimmunity1-4. Crucial for T helper17 (Th17) cells in vivo5,6, IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-β1 have been argued to be the factors responsible for initiating specification7-10. Herein, we show that Th17 differentiation occurs in the absence of TGF-β signaling. Neither IL-6 nor IL-23 alone efficiently generated Th17 cells; however, these cytokines in combination with IL-1β effectively induced IL-17 production in naïve precursors, independently of TGF-β. Epigenetic modification of the Il17a/Il17f and Rorc promoters proceeded without TGF-β1, allowing the generation of cells that co-expressed Rorγt and T-bet. T-bet+Rorγt+ Th17 cells are generated in vivo during experimental allergic encephalomyelitis (EAE), and adoptively transferred Th17 cells generated with IL-23 in the absence of TGF-β1 were more pathogenic in this experimental disease. These data suggest a new model for Th17 differentiation. Consistent with genetic data linking the IL23R with autoimmunity, our findings re-emphasize the role of IL-23 and therefore have important implications for the development of new therapies. Mouse T helper 17 cell differentiation with or without TGFB

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Genome-wide maps of chromatin state and KAP1 occupancy in KRAB zinc finger protein (KRAB-ZFP) gene cluster KO ES cells and testis

Project description:We have shown that many mouse KRAB-ZFPs target retrotransposons which are generally marked by H3K9me3 and KAP1 in ES cells. To test whether these KRAB-ZFPs are require to establish and maintain repressive chromatin marks at these elements, we performed ChIP-seq with antibodies against KAP1 (2 KRAB-ZFP cluster KOs) and H3K9me3 (5 KRAB-ZFP cluster KOs). We show that KRAB-ZFP targeted retrotransposons show reduced KAP1 binding and H3K9me3 in these KO ES cells. Furthermore, we performed ChIP-seq with antibodies against histone modifications typical for promoters and enhancers in Chr4-cl KO ES cells and testis. We show that, in ES cells, ETn retrotransposons gain signatures of active enhancers which acts on earby gene expression. In testis, a handful of different retrotransposons gain enhancer marks, although to a lesser degree. In conclusion, our data shows that KRAB-ZFPs are required to maintain H3K9me3 at retrotransposons in ES cells and to prevent some retrotransposons of becoming enhancers that affect gene expression patterns.

2019-06-27 | GSE115286 | GEO

Genome-wide analysis of DNA methylation in KRAB-ZFP cluster KO ES cells

Project description:We report a retrotransposon-specific loss of CpG methylation in chromosome 4 KRAB-ZFP cluster (Chr4-cl) KO ES cells that are cultivated in conditions that induce DNA hypomethylation. The retrotransposon groups with the strongest DNA methylation loss are the main targets of the KRAB-ZFPs within the deleted gene cluster indicating that these KRAB-ZFPs prevent complete DNA demethylation at retrotransposons during global DNA demethylation.

2019-06-27 | GSE115289 | GEO

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