title: DNA replication timing is maintained genome-wide in primary human myoblasts independent of D4Z4 contraction in FSH muscular dystrophy.
abstract: Facioscapulohumeral muscular dystrophy (FSHD) is linked to contraction of an array of tandem 3.3-kb repeats (D4Z4) at 4q35.2 from 11-100 copies to 1-10 copies. The extent to which D4Z4 contraction at 4q35.2 affects overall 4q35.2 chromatin organization remains unclear. Because DNA replication timing is highly predictive of long-range chromatin interactions, we generated genome-wide replication-timing profiles for FSHD and control myogenic precursor cells. We compared non-immortalized myoblasts from four FSHD patients and three control individuals to each other and to a variety of other human cell types. This study also represents the first genome-wide comparison of replication timing profiles in non-immortalized human cell cultures. Myoblasts from both control and FSHD individuals all shared a myoblast-specific replication profile. In contrast, male and female individuals were readily distinguished by monoallelic differences in replication timing at DXZ4 and other regions across the X chromosome affected by X inactivation. We conclude that replication timing is a robust cell-type specific feature that is unaffected by FSHD-related D4Z4 contraction.
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, Florida, United States of America.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Pope
authors.forename: Koji
authors.initials: K
authors.lastname: Tsumagari
authors.forename: Dana
authors.initials: D
authors.lastname: Battaglia
authors.forename: Tyrone
authors.initials: T
authors.lastname: Ryba
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hiratani
authors.forename: Melanie
authors.initials: M
authors.lastname: Ehrlich
authors.forename: David M
authors.initials: DM
authors.lastname: Gilbert
mesh_terms: D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D042522:DNA Replication Timing / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000235:genetics* / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism*; D020080:Tandem Repeat Sequences / Q000235:genetics*; D055815:Young Adult
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