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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

SUBMITTER: Julien Duc

PROVIDER: E-GEOD-74278 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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.

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