Expression atlas of the multivalent epigenetic regulator Brpf1 and its requirement for survival of mouse embryos

Epigenetics. 2014 Jun;9(6):860-72. doi: 10.4161/epi.28530. Epub 2014 Mar 19.

Abstract

Bromodomain- and PHD finger-containing protein 1 (BRPF1) is a unique epigenetic regulator that contains multiple structural domains for recognizing different chromatin modifications. In addition, it possesses sequence motifs for forming multiple complexes with three different histone acetyltransferases, MOZ, MORF, and HBO1. Within these complexes, BRPF1 serves as a scaffold for bridging subunit interaction, stimulating acetyltransferase activity, governing substrate specificity and stimulating gene expression. To investigate how these molecular interactions are extrapolated to biological functions of BRPF1, we utilized a mouse strain containing a knock-in reporter and analyzed the spatiotemporal expression from embryos to adults. The analysis revealed dynamic expression in the extraembryonic, embryonic, and fetal tissues, suggesting important roles of Brpf1 in prenatal development. In support of this, inactivation of the mouse Brpf1 gene causes lethality around embryonic day 9.5. After birth, high expression is present in the testis and specific regions of the brain. The 4-dimensional expression atlas of mouse Brpf1 should serve as a valuable guide for analyzing its interaction with Moz, Morf, and Hbo1 in vivo, as well as for investigating whether Brpf1 functions independently of these three enzymatic epigenetic regulators.

Keywords: BRPF1; KAT6A; KAT6B; KAT7; epigenetic reader; histone acetyltransferase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • DNA-Binding Proteins
  • Embryo Loss / genetics
  • Embryo, Mammalian / metabolism*
  • Epigenesis, Genetic*
  • Female
  • Fetus / metabolism
  • Gene Expression Profiling*
  • Gene Expression Regulation, Developmental
  • Histone Acetyltransferases / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organ Specificity

Substances

  • Adaptor Proteins, Signal Transducing
  • BRPF1 protein, mouse
  • Carrier Proteins
  • DNA-Binding Proteins
  • Histone Acetyltransferases
  • Kat7 protein, mouse
  • MOZ protein, mouse