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Nucleic Acids Res. 2019 Jan 25;47(2):700-715. doi: 10.1093/nar/gky1148.

MIR sequences recruit zinc finger protein ZNF768 to expressed genes.

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Department of Molecular Epigenetics, Helmholtz Center Munich and Center for Integrated Protein Science Munich (CIPSM), Marchioninistrasse 25, 81377 Munich, Germany.
Institute for Informatics, Ludwig-Maximilians-Universität München, Amalienstrasse 17, 80333 Munich, Germany.
Institut de Génétique Moléculaire de Montpellier (IGMM), Univ Montpellier, CNRS-UMR5535, Montpellier, France.
Biomedical Center Munich, ZFP, Großhadener Strasse 9, 82152 Planegg-Martinsried, Germany.
Laboratory for Functional Genome Analysis (LAFUGA) at the Gene Center, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.
Institute of Structural Biology, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
Department of Biochemistry and Molecular Pharmacology, New York University Langone School of Medicine, New York, NY 10016, USA.
Howard Hughes Medical Institute, New York University Langone School of Medicine, New York, NY 10016, USA.


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.

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