Department of Biological Science, Florida State University, Tallahassee, Florida, United States of America.
PLoS One. 2011;6(11):e27413. doi: 10.1371/journal.pone.0027413. Epub 2011 Nov 11.
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.
面肩肱型肌营养不良症（FSHD）与 4q35.2 处的一连串串联 3.3kb 重复（D4Z4）的收缩有关，其数量从 11-100 个拷贝减少到 1-10 个拷贝。4q35.2 处 D4Z4 收缩对整体 4q35.2 染色质组织的影响仍不清楚。由于 DNA 复制时间高度预测长距离染色质相互作用，我们为 FSHD 和对照肌原性前体细胞生成了全基因组复制时间图谱。我们将来自四位 FSHD 患者和三位对照个体的非永生化成肌细胞彼此进行比较，并与多种其他人类细胞类型进行了比较。这项研究也是首次在非永生化人类细胞培养物中进行全基因组复制时间图谱的比较。来自对照和 FSHD 个体的成肌细胞均具有成肌细胞特异性的复制图谱。相比之下，男性和女性个体通过 X 染色体失活影响的 DXZ4 和其他区域的单等位基因复制时间差异很容易区分开来。我们得出的结论是，复制时间是一种稳健的细胞类型特异性特征，不受 FSHD 相关 D4Z4 收缩的影响。
