TY  - JOUR
A1  - Hildebrand, Daniela
A1  - Tiefenbach, Jens
A1  - Heinzel, Thorsten
A1  - Grez, Manuel
A1  - Maurer, Alexander B.
T1  - Multiple regions of ETO cooperate in transcriptional repression
T2  - Journal of biological chemistry
N2  - 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.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/75990
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-759903
SN  - 0021-9258
VL  - 276.2001
IS  - 13
SP  - 9889
EP  - 9895
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -