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ChIP-exo of human KRAB-ZNFs transduced in HEK 293T cells and KAP1 in hES H1 cells

ABSTRACT: Encoded in the hundreds by the human genome, KRAB-containing zinc finger proteins (KRAB-ZFPs) constitute a rapidly evolving family of transcription factors with largely undefined functions. Here, by a combination of phylogenetic and genomic approaches, we retrace the evolutionary history of KRAB-ZFP genes and define the genomic targets of their human products. Through in silico analysis of 207 vertebrate genomes and chromatin immunoprecipitation / deep sequencing characterization of 257 human KRAB-ZFPs, we identify the root of the family in an early Devonian ancestor of tetrapods, describe its diversity amongst these species, and reveal that the majority of its human members primarily recognize transposable elements. Furthermore, by dissecting the timeline and modalities of interactions between human KRAB-ZFPs and their targets, we provide evidence strongly suggesting that these proteins, rather than just engaged in an evolutionary arms race against transposable elements, exploit these invaders as regulatory platforms for the benefit of the host.

ORGANISM(S): Homo sapiens

PROVIDER: GSE78099 | GEO | 2017/03/06

SECONDARY ACCESSION(S): PRJNA312613

REPOSITORIES: GEO

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Genome-wide binding patterns of murine KRAB zinc finger proteins

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

Chip-exo and Chip-seq of human KRAB-ZNFs transduced in HEK 293T cells

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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.

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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.

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

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

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