Multiple regions of ETO cooperate in transcriptional repression

  • In acute myeloid leukemias (AMLs) with t(8;21), the transcription factor AML1 is juxtaposed to the zinc finger nuclear protein ETO (Eight-Twenty-One), resulting in transcriptional repression of AML1 target genes. ETO has been shown to interact with corepressors, such as N-CoR and mSin3A to form complexes containing histone deacetylases. To define regions of ETO required for maximal repressor activity, we analyzed amino-terminal deletions in a transcriptional repression assay. We found that ETO mutants lacking the first 236 amino acids were not affected in their repressor activity, whereas a further deletion of 85 amino acids drastically reduced repressor function and high molecular weight complex formation. This latter mutant can still homodimerize and bind to N-CoR but shows only weak binding to mSin3A. Furthermore, we could show that a "core repressor domain" comprising nervy homology region 2 and its amino- and carboxyl-terminal flanking sequences recruits mSin3A and induces transcriptional repression. These results suggest that mSin3A and N-CoR bind to ETO independently and that both binding sites cooperate to maximize ETO-mediated transcriptional repression. Thus, ETO has a modular structure, and the interaction between the individual elements is essential for the formation of a stable repressor complex and efficient transcriptional repression.

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Metadaten
Author:Daniela HildebrandGND, Jens Tiefenbach, Thorsten HeinzelORCiDGND, Manuel GrezGND, Alexander B. MaurerGND
URN:urn:nbn:de:hebis:30:3-759903
DOI:https://doi.org/10.1074/jbc.M010582200
ISSN:0021-9258
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/11150306
Parent Title (English):Journal of biological chemistry
Publisher:American Society for Biochemistry and Molecular Biology Publications
Place of publication:Bethesda, Md
Document Type:Article
Language:English
Date of Publication (online):2021/01/04
Year of first Publication:2001
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2024/04/25
Volume:276.2001
Issue:13
Page Number:7
First Page:9889
Last Page:9895
Institutes:Angeschlossene und kooperierende Institutionen / Georg-Speyer-Haus
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International