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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.

SUBMITTER: Resnick R 

PROVIDER: S-EPMC6886682 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Resnick Rebecca R   Wong Chao-Jen CJ   Hamm Danielle C DC   Bennett Sean R SR   Skene Peter J PJ   Hake Sandra B SB   Henikoff Steven S   van der Maarel Silvère M SM   Tapscott Stephen J SJ  

Cell reports 20191101 7


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-indu  ...[more]

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