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

Ferdinand M. Huber, Sarah M. Greenblatt, Andrew M. Davenport, Concepcion Martinez, Ye Xu, Ly P. Vu, Stephen D Nimer, André Hoelz

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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-Å 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.

Original languageEnglish (US)
Pages (from-to)6016-6021
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number23
DOIs
StatePublished - Jun 6 2017

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Histones
Plant Structures
Acute Myeloid Leukemia
Mutagenesis
Chromatin
Tail
Proteins

Keywords

  • Isothermal titration calorimetry
  • Myeloid differentiation
  • Protein-protein interaction
  • Tandem PHD finger
  • X-ray crystallography

ASJC Scopus subject areas

  • General

Cite this

Histone-binding of DPF2 mediates its repressive role in myeloid differentiation. / Huber, Ferdinand M.; Greenblatt, Sarah M.; Davenport, Andrew M.; Martinez, Concepcion; Xu, Ye; Vu, Ly P.; Nimer, Stephen D; Hoelz, André.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 23, 06.06.2017, p. 6016-6021.

Research output: Contribution to journalArticle

Huber, Ferdinand M. ; Greenblatt, Sarah M. ; Davenport, Andrew M. ; Martinez, Concepcion ; Xu, Ye ; Vu, Ly P. ; Nimer, Stephen D ; Hoelz, André. / Histone-binding of DPF2 mediates its repressive role in myeloid differentiation. In: Proceedings of the National Academy of Sciences of the United States of America. 2017 ; Vol. 114, No. 23. pp. 6016-6021.
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