Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA188562 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:KRAB/KAP1-microRNA cascade regulates erythropoiesis through the stage-specific control of mitophagy [Seq]
| PRJNA188561 | ENA
Project description:We used ChIP-seq to assess how abolition of KRAB binding by KAP1 (through structure-guided mutations in the KAP1-KRAB binding interface) changed the distribution of KAP1 on chromatin genome-wide.
2022-10-10 | GSE215015 | GEO
Project description:We used CUT&RUN to assess how abolition of KRAB binding by KAP1 (through structure-guided mutations in the KAP1-KRAB binding interface) changed the distribution of H3K9me3 epigenetic mark genome-wide.
2022-10-10 | GSE215014 | GEO
Project description:Krüppel-associated box (KRAB)-containing zinc finger proteins (KZFPs) represent the largest family of human transcription factors. The majority of its members bind to Transposable Elements (TEs), which they repress through the recruitment of the repressor KAP1 to their conserved KRAB domain. In addition to this recognized role, some KZFPs seem to favor different types of loci such as transcription start sites or display diverse functions such as imprinting and gene regulation. Intriguingly, a subset of KZFPs was shown not to recruit the corepressor KAP1. Therefore, we sought to get a better picture of KZFPs putative roles and their association with KAP1. In order to do so, we generated the interactomes of 101 KZFPs through Affinity Purification followed by Mass Spectrometry (AP-MS).
2019-06-04 | PXD011322 | Pride
Project description:KAP1 is overexpressed in breast cancer. To determine KAP1 regulated genes, we performed microarray analysis of gene expression in KAP1 depleted breast cancer cells MDA-MB-231LN. The transcriptional regulator TRIM28/KAP1 plays an important role in development, stem cell self-renewal, chromatin organization and the DNA damage response. KAP1 is an essential co-repressor for KRAB zinc finger proteins (KRAB-ZNFs). Though KRAB-ZNFs represent the largest family of human transcription factors, their biological functions are largely unknown. Using the conserved zinc fingers linker region (ZnFL) as antigen, we have developed a ZnFL antibody that recognizes multiple KRAB-ZNFs. We showed that KAP1 and many KRAB-ZNFs were overexpressed in human breast cancers and breast cancer cell lines. In addition, an active SUMOylated form of KAP1 was markedly increased in breast cancer cells. Furthermore, KAP1 depletion in breast cancer cell lines reduced cell proliferation and inhibited tumor growth and metastasis of tumor xenografts. Conversely, KAP1 overexpression stimulated cell proliferation and tumor growth. KAP1 knockdown led to down-regulation of genes previously linked to tumor progression and metastasis, including PTGS2/COX2, EREG, CD44, MMP1 and MMP2. Interestingly, KAP1 depletion or genomic deletion led to dramatic down-regulation of multiple KRAB-ZNF proteins due in part to their increased degradation. KAP1-dependent stabilization of KRAB-ZNFs required a direct KRAB-ZNF-KAP1 interaction. These results establish KAP1 as a positive regulator of multiple KRAB-ZNFs and an important factor in the development of breast cancer. 7 total samples were analyzed. Stable sublines of MDA-MB-231LN cells expressing control non-targeting shRNA (Scr, 3 biological replicates) and two different shRNAs against KAP1 (KAP1-3, 2 biological replicates and KAP1-4, 2 biological replicates) from doxycycline-inducible pTRIPZ vector were cultured in the presence of 0.5 ug/ml doxycycline for 7 days to induce shRNA expression. Cells were lysed and total RNA was isolated using mirVana miRNA isolation kit (Ambion) in the WVU Genomics Core Facility.
2014-09-23 | E-GEOD-61639 | biostudies-arrayexpress
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
Project description:KAP1 (TRIM28) is a transcriptional regulator in embryonic development that controls stem cell self-renewal, chromatin organization and the DNA damage response, acting as an essential co-repressor for KRAB family zinc finger proteins (KRAB-ZNF). To gain insight into the function of this large gene family, we developed an antibody that recognizes the conserved zinc fingers linker region (ZnFL) in multiple KRAB-ZNF. Here we report that the expression of many KRAB-ZNF along with active SUMOlyated KAP1 is elevated widely in human breast cancers. KAP1 silencing in breast cancer cells reduced proliferation and inhibited the growth and metastasis of tumor xenografts. Conversely, KAP1 overexpression stimulated cell proliferation and tumor growth. In cells where KAP1 was silenced, we identified multiple downregulated genes linked to tumor progression and metastasis, including EREG/epiregulin, PTGS2/COX2, MMP1, MMP2 and CD44, along with downregulation of multiple KRAB-ZNF proteins. KAP1-dependent stabilization of KRAB-ZNF required direct interactions with KAP1. Together, our results show that KAP1-mediated stimulation of multiple KRAB-ZNF contributes to the growth and metastasis of breast cancer.
2014-09-23 | GSE61639 | GEO
Project description:The modulation of chromatin status at specific genomic loci controls lymphoid differentiation. Here, we investigated the role played in this process by KAP1, the universal cofactor of KRAB-containing Zinc Finger Proteins (KRAB-ZFPs), a tetrapod-restricted family of transcriptional repressors. T cell-specific Kap1 knockout mice displayed a significant expansion of immature thymocytes and imbalances in the ratios of mature T cells in the thymus and the spleen, with impaired responses to TCR stimulation. Transcriptome and chromatin studies revealed that KAP1 directly controls the expression of a number of genes involved in TCR and cytokine signalling, among which Traf1 and FoxO1, and is strongly associated with cis-acting regulatory elements marked by the H3K9me3 repressive mark on the genome of thymic T cells. Likely responsible for tethering KAP1 to at least part of its genomic targets, a small number of KRAB/ZFPs are selectively expressed in T lymphoid cells. These results reveal the so far unsuspected yet important role of KRAB/KAP1-mediated epigenetic regulation in T lymphocyte differentiation and activation. Cells were harvested form the thymus of 3 CD4-Cre/Kap1flox (KAP1 KO in the T lineage) mice and 3 wt/Kap1flox littermate controls
2012-12-16 | E-GEOD-34447 | biostudies-arrayexpress
Project description:Chromatin remodelling at specific genomic loci controls lymphoid differentiation. Here, we investigated the role played in this process by Kruppel-Associated Box (KRAB)- Associated Protein 1 (KAP1), the universal cofactor of KRAB-zinc finger proteins (-ZFPs), a tetrapod-restricted family of transcriptional repressors. T cell-specific Kap1-deleted mice displayed a significant expansion of immature thymocytes, imbalances in CD4+/CD8+ cell ratios and impaired responses to TCR stimulation when compared to littermate KAP1 control mice. Transcriptome and chromatin studies revealed that KAP1 binds T cell-specific cis-acting regulatory elements marked by the H3K9me3 repressive mark and enriched in Ikaros/NuRD complexes. Also, KAP1 directly controls the expression of several genes involved in TCR and cytokine signalling. Among these, regulation of FoxO1 seems to play a major role in this system. Likely responsible for tethering KAP1 to at least part of its genomic targets, a small number of KRAB-ZFPs are selectively expressed in T lymphoid cells. These results reveal the so-far unsuspected yet important role of KAP1-mediated epigenetic regulation in T lymphocyte differentiation and activation. Examination of KAP1 binding sites and H3K9me3-enriched regions in wild type and KAP1 KO mouse thymocytes.
2012-12-16 | E-GEOD-38579 | biostudies-arrayexpress