DUX4-Induced Histone Variants H3.X and H3.Y Mark DUX4 Target Genes for Expression

• Main Authors: Rebecca Resnick, Chao-Jen Wong, Danielle C. Hamm, Sean R. Bennett, Peter J. Skene, Sandra B. Hake, Steven Henikoff, Silvère M. van der Maarel, Stephen J. Tapscott
• Format: Article
• Language: English
• Published: Elsevier 2019-11-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124719313257

Summary: The DUX4 transcription factor is briefly expressed in the early 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 histone variants H3.X and H3.Y. We have used a myoblast cell line with doxycycline-inducible DUX4 to show that 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 H3.X/Y as a chromatin mechanism that facilitates the expression of DUX4 target genes subsequent to a brief pulse of DUX4 expression. : Resnick et al. show that the DUX4-induced histone variants, H3.X and H3.Y, incorporate into the chromatin of DUX4-induced genes, making them more sensitive to subsequent expression. This suggests a mechanism for how the brief expression of DUX4 can establish a memory of its transcriptional network. Keywords: DUX4, H3.X, H3.Y, facioscapulohumeral dystrophy, transcription, histone variants