DUX4-induced histone variants H3.X and H3.Y mark DUX4 target genes for expression

Abstract

The DUX4 transcription factor is briefly expressed in the cleavage-stage embryo where it induces an early wave of zygotic gene transcription; whereas its mis-expression in skeletal muscle causes the muscular dystrophy facioscapulohumeral dystrophy (FSHD). Here, we show that DUX4 induces the expression of the histones H3.X and H3.Y. These histone variants are incorporated throughout the body of DUX4-induced genes. Following a brief pulse of DUX4, these histones contribute to greater perdurance and to enhanced re-activation of DUX4 target gene expression. These findings provide a model for a DUX4-induced chromatin memory that facilitates the expression of its target genes subsequent to a brief pulse of DUX4 expression.