MIR sequences recruit zinc finger protein ZNF768 to expressed genes

Abstract Mammalian-wide interspersed repeats (MIRs) are retrotransposed elements of mammalian genomes. Here, we report the specific binding of zinc finger protein ZNF768 to the sequence motif GCTGTGTG (N20) CCTCTCTG in the core region of MIRs. ZNF768 binding is preferentially associated with euchrom...

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Bibliographic Details
Published in:Nucleic acids research 2019-01, Vol.47 (2), p.700-715
Main Authors: Rohrmoser, Michaela, Kluge, Michael, Yahia, Yousra, Gruber-Eber, Anita, Maqbool, Muhammad Ahmad, Forné, Ignasi, Krebs, Stefan, Blum, Helmut, Greifenberg, Ann Katrin, Geyer, Matthias, Descostes, Nicolas, Imhof, Axel, Andrau, Jean-Christophe, Friedel, Caroline C, Eick, Dirk
Format: Article
Language:English
Subjects:
Binding Sites
Cell Line, Tumor
Cell Survival
DNA - chemistry
DNA - metabolism
Euchromatin - metabolism
Gene Expression Regulation
Gene regulation, Chromatin and Epigenetics
Humans
Nucleotide Motifs
Repetitive Sequences, Nucleic Acid
Retroelements
Transcription Factors - chemistry
Transcription Factors - metabolism
Transcription, Genetic
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Summary:Abstract Mammalian-wide interspersed repeats (MIRs) are retrotransposed elements of mammalian genomes. Here, we report the specific binding of zinc finger protein ZNF768 to the sequence motif GCTGTGTG (N20) CCTCTCTG in the core region of MIRs. ZNF768 binding is preferentially associated with euchromatin and promoter regions of genes. Binding was observed for genes expressed in a cell type-specific manner in human B cell line Raji and osteosarcoma U2OS cells. Mass spectrometric analysis revealed binding of ZNF768 to Elongator components Elp1, Elp2 and Elp3 and other nuclear factors. The N-terminus of ZNF768 contains a heptad repeat array structurally related to the C-terminal domain (CTD) of RNA polymerase II. This array evolved in placental animals but not marsupials and monotreme species, displays species-specific length variations, and possibly fulfills CTD related functions in gene regulation. We propose that the evolution of MIRs and ZNF768 has extended the repertoire of gene regulatory mechanisms in mammals and that ZNF768 binding is associated with cell type-specific gene expression.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gky1148