Histone-binding of DPF2 mediates its repressive role in myeloid differentiation

作者：Huber Ferdinand M; Greenblatt Sarah M; Davenport Andrew M; Martinez Concepcion; Xu Ye; Vu Ly P; Nimer Stephen D^*; Hoelz Andre^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2017, 114(23): 6016-6021.

DOI：10.1073/pnas.1700328114

• X-ray crystallography
• myeloid differentiation
• tandem PHD finger
• isothermal titration calorimetry
• protein-protein interaction

Double plant homeodomain finger 2 (DPF2) is a highly evolutionarily conserved member of the d4 protein family that is ubiquitously expressed in human tissues and was recently shown to inhibit the myeloid differentiation of hematopoietic stem/progenitor and acute myelogenous leukemia cells. Here, we present the crystal structure of the tandem plant homeodomain finger domain of human DPF2 at 1.6-angstrom resolution. We show that DPF2 interacts with the acetylated tails of both histones 3 and 4 via bipartite binding pockets on the DPF2 surface. Blocking these interactions through targeted mutagenesis of DPF2 abolishes its recruitment to target chromatin regions as well as its ability to prevent myeloid differentiation in vivo. Our findings suggest that the histone binding of DPF2 plays an important regulatory role in the transcriptional program that drives myeloid differentiation.

• 出版日期2017-6-6