Facioscapulohumeral muscular dystrophy (FSHD), a progressive myopathy that afflicts individuals of all ages, provides a powerful model of the complex interplay between genetic and epigenetic mechanisms of chromatin regulation. FSHD is caused by dysregulation of a macrosatellite repeat, either by contraction of the repeat or by mutations in silencing proteins. Both cases lead to chromatin relaxation and, in the context of a permissive allele, aberrant expression of the DUX4 gene in skeletal muscle. DUX4 is a pioneer transcription factor that activates a program of gene expression during early human development, after which its expression is silenced in most somatic cells. When misexpressed in FSHD skeletal muscle, the DUX4 program leads to accumulated muscle pathology. Epigenetic regulators of the disease locus represent particularly attractive therapeutic targets for FSHD, as many are not global modifiers of the genome, and altering their expression or activity should allow correction of the underlying defect.

中文翻译：

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面肩肱型肌营养不良症的遗传学和表观遗传学。


面肩肱型肌营养不良症 (FSHD) 是一种进行性肌病，困扰所有年龄段的个体，它为染色质调控的遗传和表观遗传机制之间复杂的相互作用提供了一个强有力的模型。 FSHD 是由大卫星重复序列的失调引起的，要么是重复序列的收缩，要么是沉默蛋白的突变。这两种情况都会导致染色质松弛，并且在允许等位基因的情况下，骨骼肌中 DUX4 基因的异常表达。 DUX4 是一种先驱转录因子，在人类早期发育过程中激活基因表达程序，此后其表达在大多数体细胞中被沉默。当 DUX4 程序在 FSHD 骨骼肌中错误表达时，会导致肌肉病理累积。疾病位点的表观遗传调节因子代表了 FSHD 特别有吸引力的治疗靶点，因为许多调节因子不是基因组的全局修饰因子，改变它们的表达或活性应该可以纠正潜在的缺陷。