dna replication timing is maintained genome-wide in primary human myoblasts independent of d4z4 contraction in fsh muscular dystrophydna复制时间保持全基因组在人类肌母细胞主要独立fsh d4z4收缩的肌肉萎缩症.pdfVIP

DNA Replication Timing Is Maintained Genome-Wide in Primary Human Myoblasts Independent of D4Z4 Contraction in FSH Muscular Dystrophy 1 2 1 1 1¤ 2 Benjamin D. Pope , Koji Tsumagari , Dana Battaglia , Tyrone Ryba , Ichiro Hiratani , Melanie Ehrlich *, David M. Gilbert1* 1 Department of Biological Science, Florida State University, Tallahassee, Florida, United States of America, 2 Human Genetics Program, Department of Biochemistry, and Tulane Cancer Center, Tulane Medical School, New Orleans, Louisiana, United States of America 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 repl