Thermodynamic investigation of DNA-binding affinity of wild-type and mutant transcription factor RUNX1.

ABSTRACT: Transcription factor RUNX1 and its binding partner CBFβ play a critical role in gene regulation for hematopoiesis. Mutations of RUNX1 cause ~10% of acute myeloid leukemia (AML) with a particularly poor prognosis. The current paradigm for the leukemogenesis is that insufficient activity of wild-type (WT) RUNX1 impairs hematopoietic differentiation. The majority of mutant RUNX1 proteins lose the DNA-binding affinity and inhibit WT RUNX1 by depletion of CBFβ. Here, isothermal titration calorimetry (ITC) was used to quantitatively study the interactions of WT and three clinical mutant RUNX1, CBFβ and DNA. Our data show that the binding of RUNX1 to DNA is enthalpy-driven, and the affinity decreases in the order of WT > S114L > R139Q >> K83E, which support previous observations and conclusion. T

SUBMITTER: Wu F 

PROVIDER: S-EPMC6497270 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature