Systematic identification and characterization of repressive domains in Drosophila transcription factors.

Autor: Klaus L; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.; Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna, Vienna, Austria., de Almeida BP; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.; Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna, Vienna, Austria., Vlasova A; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria., Nemčko F; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.; Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna, Vienna, Austria., Schleiffer A; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.; Institute of Molecular Biotechnology (IMBA), Vienna BioCenter (VBC), Vienna, Austria., Bergauer K; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria., Hofbauer L; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.; Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna, Vienna, Austria., Rath M; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria., Stark A; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.; Medical University of Vienna, Vienna BioCenter (VBC), Vienna, Austria.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2023 Feb 01; Vol. 42 (3), pp. e112100. Date of Electronic Publication: 2022 Dec 22.
DOI: 10.15252/embj.2022112100
Abstrakt: All multicellular life relies on differential gene expression, determined by regulatory DNA elements and DNA-binding transcription factors that mediate activation and repression via cofactor recruitment. While activators have been extensively characterized, repressors are less well studied: the identities and properties of their repressive domains (RDs) are typically unknown and the specific co-repressors (CoRs) they recruit have not been determined. Here, we develop a high-throughput, next-generation sequencing-based screening method, repressive-domain (RD)-seq, to systematically identify RDs in complex DNA-fragment libraries. Screening more than 200,000 fragments covering the coding sequences of all transcription-related proteins in Drosophila melanogaster, we identify 195 RDs in known repressors and in proteins not previously associated with repression. Many RDs contain recurrent short peptide motifs, which are conserved between fly and human and are required for RD function, as demonstrated by motif mutagenesis. Moreover, we show that RDs that contain one of five distinct repressive motifs interact with and depend on different CoRs, such as Groucho, CtBP, Sin3A, or Smrter. These findings advance our understanding of repressors, their sequences, and the functional impact of sequence-altering mutations and should provide a valuable resource for further studies.
(© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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