Faculty, Staff and Student Publications
Publication Date
2-1-2023
Journal
Journal of Biological Chemistry
DOI
10.1016/j.jbc.2023.102885
PMID
36626981
PMCID
PMC9932118
PubMedCentral® Posted Date
January 2023
PubMedCentral® Full Text Version
Post-print
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.
Keywords
Humans, Cell Line, Tumor, DNA-Binding Proteins, Leukemia, Myeloid, Acute, Mutation, Transcription Factors, Zinc Fingers, Protein Domains, Protein Binding
Published Open-Access
yes
Recommended Citation
Ren, Ren; Horton, John R; Chen, Qin; et al., "Structural Basis for Transcription Factor ZBTB7A Recognition of DNA and Effects of ZBTB7A Somatic Mutations That Occur in Human Acute Myeloid Leukemia" (2023). Faculty, Staff and Student Publications. 1075.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/1075
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