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KAP1 targets actively transcribed genomic loci to exert pleomorphic effects on RNA Polymerase II- and III-mediated expression [RNA-Seq, small RNA-Seq]

ABSTRACT: KAP1 (KRAB-associated protein 1) is best known as a co-repressor responsible for inducing heterochromatin formation notably at transposable elements. However, it has also been observed to bind the transcription start site of actively expressed genes. To address this paradox, we characterized the protein interactome of KAP1 in human embryonic stem cells and in the K562 erythro-leukemia cell line. We found that the regulator can associate with a wide range of nucleic acid binding proteins, nucleosome remodelers, chromatin modifiers and other transcription modulators. We further determined that KAP1 is recruited not only at actively transcribed polymerase II promoters, but also at genetic units driven by polymerase III, for instance tRNA genes. While KAP1 depletion induced a mild downregulation of these genes, at PolII-transcribed units it resulted in pleomorphic effects, whether expression of these genes was normally constitutive or inducible, consistent with the breadth of possible KAP1 interactors

ORGANISM(S): Mus musculus

PROVIDER: GSE106975 | GEO | 2018/11/16

REPOSITORIES: GEO

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KAP1 targets actively transcribed genomic loci to exert pleomorphic effects on RNA Polymerase II- and III-mediated expression [ChIP-Seq]

Project description:KAP1 (KRAB-associated protein 1) is best known as a co-repressor responsible for inducing heterochromatin formation notably at transposable elements. However, it has also been observed to bind the transcription start site of actively expressed genes. To address this paradox, we characterized the protein interactome of KAP1 in human embryonic stem cells and in the K562 erythro-leukemia cell line. We found that the regulator can associate with a wide range of nucleic acid binding proteins, nucleosome remodelers, chromatin modifiers and other transcription modulators. We further determined that KAP1 is recruited not only at actively transcribed polymerase II promoters, but also at genetic units driven by polymerase III, for instance tRNA genes. While KAP1 depletion induced a mild downregulation of these genes, at PolII-transcribed units it resulted in pleomorphic effects, whether expression of these genes was normally constitutive or inducible, consistent with the breadth of possible KAP1 interactors

2018-11-16 | GSE106974 | GEO

KAP1 targets actively transcribed genomic loci to exert pleomorphic effects on RNA Polymerase II- and III-mediated expression

Project description:KAP1 targets actively transcribed genomic loci to exert pleomorphic effects on RNA Polymerase II- and III-mediated expression

| PRJNA418703 | ENA

KAP1 targets actively transcribed genomic loci to exert pleomorphic effects on RNA Polymerase II- and III-mediated expression [ChIP-Seq]

Project description:KAP1 targets actively transcribed genomic loci to exert pleomorphic effects on RNA Polymerase II- and III-mediated expression [ChIP-Seq]

| PRJNA418708 | ENA

KAP1 targets actively transcribed genomic loci to exert pleomorphic effects on RNA Polymerase II- and III-mediated expression [RNA-Seq, small RNA-Seq]

Project description:KAP1 targets actively transcribed genomic loci to exert pleomorphic effects on RNA Polymerase II- and III-mediated expression [RNA-Seq, small RNA-Seq]

| PRJNA418707 | ENA

KAP1 targets actively transcribed genomic loci to exert pleomorphic effects on RNA polymerase II activity.

Project description:KAP1 (KRAB-associated protein 1) is best known as a co-repressor responsible for inducing heterochromatin formation, notably at transposable elements. However, it has also been observed to bind the transcription start site of actively expressed genes. To address this paradox, we characterized the protein interactome of KAP1 in the human K562 erythro-leukaemia cell line. We found that the regulator can associate with a wide range of nucleic acid binding proteins, nucleosome remodellers, chromatin modifiers and other transcription modulators. We further determined that KAP1 is recruited at actively transcribed polymerase II promoters, where its depletion resulted in pleomorphic effects, whether expression of these genes was normally constitutive or inducible, consistent with the breadth of possible KAP1 interactors. This article is part of a discussion meeting issue 'Crossroads between transposons and gene regulation'.

| S-EPMC7061982 | biostudies-literature

KAP1 targets actively transcribed genomic loci to exert pleomorphic effects on RNA Polymerase II- and III-mediated expression

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

2018-11-16 | GSE106976 | GEO

Functional analysis of Kap1 genomic recruitment

Project description:A current model for the genomic recruitment of Kap1 is via its interaction with KRAB domain-containing zinc finger transcription factors. We have performed ChIP-seq for various mutant KAP1 proteins and shown that this recruitment mechanism mediates binding of KAP1 only to the 3M-CM-"M-BM-^@M-BM-^Y ends of zinc finger genes and that other factors are involved in recruiting KAP1 to promoter regions. 17 total ChIP-seq datasets; three different FLAG-KAP1 mutants, one FLAG-KAP1 wild type, and four different Input datasets from 4 different stable cell lines derived from HEK293 cells: 1 FLAG-KAP1 wild type dataset and 1 Input dataset done from HEK293 stable cells; 1 FLAG-KAP1 HP1BDmut dataset and 1 Input dataset done from HEK293 stable cells, 1 FLAG-KAP1 N-ter RBCC{delta}mut dataset and 1 Input dataset done from HEK293 stable cells, 1 FLAG-KAP1 C-ter PB{delta}mut dataset and 1 Input dataset done from HEK293 stable cells. One FLAG-KAP1 N/C-ter (RBCC+PB){delta}mut dataset done from T-REx HEK293 stable cells. One endogenous KAP1 dataset done from HEK293 cells. Two independent ELK4 datasets done from duplicate HEK293 cells. One endogenous Kap1 dataset and one Input dataset from a stable cell line derived from U2OS cells.

2011-05-24 | E-GEOD-27929 | biostudies-arrayexpress

Gene expression profile of wt-, S473A- and S473D-KAP1-re-expression in KAP1-depleted MDA-MB-231 cell

Project description:We study the gene regulation function of serine 473 phosphorylation of KAP1 (pS473-KAP1) in MDA-MB-231 cells. Wild type KAP1, S473A-KAP1 (phospho-acceptor site mutant) and S473D-KAP1 (phospho-mimetic mutant) are re-expressed in KAP1 knockdown cells. We analyze the gene expression profile in these three cells and find that many mitochondrial complex genes are up-regulated in S473D-KAP1 re-expressing cells. This study provides information about pS473-KAP1-regulated gene expression.

2016-11-08 | GSE63344 | GEO

KAP1 regulates Treg function and proliferation.

Project description:KAP1 is a partner of Foxp3 in Tregs. Since Treg specific KAP1 deficient mice develop autoimmune disease, KAP1 is an important factor. To address the mechanisms of KAP1 regulation in Treg function, we performed RNA-seq analysis.

2018-03-11 | GSE105128 | GEO

KAP1(TRIM28/TIF1beta) represses differentiation-inducible genes in embryonic stem cells through cooperative binding with PRC1(Ring1b/Rnf2) and derepresses pluripotency-associated genes (expression)

Project description:Embryonic stem (ES) cells express pluripotency-associated genes and repress differentiation-inducible genes. The activities of these genes are coordinately reversed during differentiation. The changes in the transcriptome upon conditional KAP1 knockout in ES cells overlapped with the changes during embryoid body formation. KAP1 repressed differentiation-inducible genes and derepressed pluripotency-associated genes in ES cells. KAP1 formed complexes with polycomb repressive complexes 1 (PRC1) through an interaction that was mediated by the KAP1 coiled-coil region. KAP1 and PRC1 bound cooperatively at the promoters of differentiation-inducible genes and repressed their transcription. In contrast, KAP1 bound the transcribed and flanking sequences of pluripotency-associated genes, did not enhance PRC1 binding, and derepressed their transcription. KAP1 had opposite effects on differentiation-inducible and pluripotency-associated gene transcription both in ES cells and in differentiating embryoid bodies. The region of KAP1 that mediated the interaction with PRC1 was required for KAP1 enhancement of PRC1 binding and for KAP1 repression of transcription at differentiation-inducible promoters. This region of KAP1 was not required for KAP1 suppression of PRC1 binding or for KAP1 derepression of transcription at pluripotency-associated promoters. The opposite effects of KAP1 on transcription of differentiation-inducible versus pluripotency-associated genes contributed to the reciprocal changes in their transcription during differentiation. Analysis of the transcript levels in mouse embryonic stem cells before and after conditional KAP fl/fl knockout

2014-05-09 | E-GEOD-56626 | biostudies-arrayexpress

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