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 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.

• 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
• Journal: Cell reports (Cell Rep) Vol. 29 Issue 7 Pg. 1812-1820.e5 (11 12 2019) ISSN: 2211-1247 [Electronic] United States
• PMID: 31722199 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• DUX4L1 protein, human
• Histones
• Homeodomain Proteins

Topics

• Cell Line
• Gene Expression Regulation
• Histones (genetics, metabolism)
• Homeodomain Proteins (genetics, metabolism)
• Humans
• Muscle, Skeletal (metabolism, pathology)
• Muscular Dystrophy, Facioscapulohumeral (genetics, metabolism, pathology)