Genome-wide maps of chromatin state and KAP1 occupancy in KRAB zinc finger protein (KRAB-ZFP) gene cluster KO ES cells and testis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA474489 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7254710.fastq.gz | Fastqsanger.gz | |||
| SRR7254720.fastq.gz | Fastqsanger.gz | |||
| SRR7254730_1.fastq.gz | Fastqsanger.gz | |||
| SRR7254730_2.fastq.gz | Fastqsanger.gz | |||
| SRR7254740.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 84 |
Similar Datasets
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
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:Mammalian genomes encode several hundred Krüppel-associated box zinc finger proteins (KRAB-ZFPs) that bind DNA in a sequence-specific manner through tandem arrays of C2H2-type zinc fingers and repress transcription via KRAB-dependent recruitment of the silencing cofactor KAP1. The KRAB-ZFP family rapidly amplified and diversified in mammals by segmental gene duplications, mutations, and zinc finger rearrangements likely in response to continued transposable element invasions, but the biological functions and in vivo requirement of these proteins has gone largely unexplored. We determined the genomic binding sites of 61 murine KRAB-ZFPs and genetically deleted five large KRAB-ZFP gene clusters encoding more than 100 of the approximately 360 mouse KRAB-ZFPs. We demonstrate that most KRAB-ZFPs bind to specific retrotransposon families and that many of these retrotransposons are transcriptionally activated in KRAB-ZFP cluster KO ESCs, licensing retrotransposon-derived enhancers to activate nearby genes.
2019-06-27 | GSE115288 | GEO
Project description:Mammalian genomes encode several hundred Krüppel-associated box zinc finger proteins (KRAB-ZFPs) that bind DNA in a sequence-specific manner through tandem arrays of C2H2-type zinc fingers and repress transcription via KRAB-dependent recruitment of the silencing cofactor KAP1. The KRAB-ZFP family rapidly amplified and diversified in mammals by segmental gene duplications, mutations, and zinc finger rearrangements likely in response to continued transposable element invasions, but the biological functions and in vivo requirement of these proteins has gone largely unexplored. Here we report the identification of the genome-wide binding profiles of 61 mouse KRAB-ZFPs by overexpression of epitope-tagged transgenes. We found that 51 of these KRAB-ZFPs target at least one retrotransposon group. Interestingly, evolutionary young and still active retrotransposons such as IAP and ETn elements are targeted by several KRAB-ZFPs which are mainly encoded within two gene clusters that are not conserved in any other sequenced species. This indicated that an evolutionary arms race drives the rapid expansion of KRAB-ZFP genes in order to restrict active retrotransposons.
2019-06-27 | GSE115287 | GEO
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.
2016-03-15 | GSE74278 | 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: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
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:Transcriptional silencing of endogenous retroviruses (ERV) defends against active retrotransposition and disease, including overproduction of non-ecotropic ERV (NEERV) envelope and resultant nephritis observed in lupus-prone mice. However, a repressor targeting NEERV loci has not yet been identified. In this study, we identified suppressor of NEERV (Snerv), a Krüppel-associated box zinc finger protein gene responsible for NEERV repression in multiple inbred mouse strains. We show that SNERV binds to the NEERV long terminal repeat and recruits the transcriptional regulator KAP1. Germline deletion of Snerv leads to increased activating chromatin modifications, transcription, and expression of envelope glycoprotein, gp70, from NEERV loci. We found that the NZB and 129 genomes, which overexpress NEERV gp70, cannot rescue defective NEERV repression in F1 crosses to Snerv-/- mice, thus mapping the long sought-after Sgp3 and Gv1 loci to Snerv and demonstrating that loss of SNERV is responsible for the overexpression of the lupus autoantigen gp70. We also found elevated expression of human ERV transcripts in lupus patients compared to healthy controls, and identify putative KRAB-ZFP genes whose expression inversely correlates with human ERV levels. Collectively, our study highlights a role for the KRAB-ZFP, Snerv, in mouse NEERV repression, and suggests similar ERV dysregulation in human lupus disease.
2019-12-31 | GSE121640 | GEO
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