RRC ID 77338
Author Ren R, Horton JR, Chen Q, Yang J, Liu B, Huang Y, Blumenthal RM, Zhang X, Cheng X.
Title Structural basis for transcription factor ZBTB7A recognition of DNA and effects of ZBTB7A somatic mutations that occur in human acute myeloid leukemia.
Journal J Biol Chem
Abstract ZBTB7A belongs to a small family of transcription factors having three members in humans (7A, 7B, and 7C). They share a BTB/POZ protein interaction domain at the amino end and a zinc-finger DNA-binding domain at the carboxyl end. They control the transcription of a wide range of genes, having varied functions in hematopoiesis, oncogenesis, and metabolism (in particular glycolysis). ZBTB7A-binding profiles at gene promoters contain a consensus G(a/c)CCC motif, followed by a CCCC sequence in some instances. Structural and mutational investigations suggest that DNA-specific contacts with the four-finger tandem array of ZBTB7A are formed sequentially, initiated from ZF1-ZF2 binding to G(a/c)CCC before spreading to ZF3-ZF4, which bind the DNA backbone and the 3' CCCC sequence, respectively. Here, we studied some mutations found in t(8;21)-positive acute myeloid leukemia patients that occur within the ZBTB7A DNA-binding domain. We determined that these mutations generally impair ZBTB7A DNA binding, with the most severe disruptions resulting from mutations in ZF1 and ZF2, and the least from a frameshift mutation in ZF3 that results in partial mislocalization. Information provided here on ZBTB7A-DNA interactions is likely applicable to ZBTB7B/C, which have overlapping functions with ZBTB7A in controlling primary metabolism.
Volume 299(2)
Pages 102885
Published 2023-2-1
DOI 10.1016/j.jbc.2023.102885
PII S0021-9258(23)00017-0
PMID 36626981
PMC PMC9932118
MeSH Cell Line, Tumor DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Humans Leukemia, Myeloid, Acute* / genetics Mutation Protein Binding / genetics Protein Domains / genetics Transcription Factors* / genetics Transcription Factors* / metabolism Zinc Fingers / genetics
IF 4.238
Resource
Human and Animal Cells HUDEP-2(RCB4557)