Cytogenetic and immuno-FISH analysis of the 4q subtelomeric region, which is associated with facioscapulohumeral muscular dystrophy.
Cytogenetic and immuno-FISH analysis of the 4q subtelomeric region, which is associated with facioscapulohumeral muscular dystrophy.
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4q 亚端粒区域的细胞遗传学和免疫 FISH 分析，该区域与面肩肱型肌营养不良症相关。
DOI：
10.1007/s00412-004-0280-x
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发表时间：
2004
期刊：
影响因子：
1.6
通讯作者：
Ehrlich,Melanie
中科院分区：
文献类型：
--
作者：
Yang,Fan;Shao,Chunbo;Vedanarayanan,Vettaikorumakankav;Ehrlich,Melanie
面肩肩周肌营养不良(FSHD)是由一个等位基因4q35.2区域3.3kb重复序列(D4Z4)的拷贝数多态排列缩短引起的。亚端粒串联阵列的这种收缩如何导致FSHD尚不清楚，但间接证据表明，短阵列对一个或多个遥远的基因有负面影响。据推测，D4Z4阵列的长度决定了该阵列和较大的近端区域是否为异染色体，从而控制基因表达。为了验证这一点，我们使用FSHD和对照成肌细胞的荧光原位杂交探针来表征4q35.2远端的下列方面：染色质染料4‘，6-二氨基-2-苯吲哚的强烈染色；与结构性异染色斑的结合；异染色质蛋白1α的结合程度；组蛋白H3赖氨酸9和赖氨酸4的甲基化；组蛋白H4赖氨酸8乙酰化；以及S相内的复制时间。我们的结果表明，在FSHD和对照成肌细胞中，4q35.2不同于构成异染色质。此外，在这些分析中，FSHD成肌细胞的等位基因4q35.2区域的行为与对照成肌细胞没有什么不同。D4Z4阵列收缩如何导致基因表达切迹的远程调控的其他模型还需要测试。
Facioscapulohumeral muscular dystrophy (FSHD) is caused by the shortening of a copy-number polymorphic array of 3.3 kb repeats (D4Z4) at one allelic 4q35.2 region. How this contraction of a subtelomeric tandem array causes FSHD is unknown but indirect evidence suggests that a short array has aciseffect on a distant gene or genes. It was hypothesized that the length of the D4Z4 array determines whether or not the array and a large proximal region are heterochromatic and thereby controls gene expression incis. To test this, we used fluorescence in situ hybridization probes with FSHD and control myoblasts to characterize the distal portion of 4q35.2 with respect to the following: intense staining with the chromatin dye 4′,6-diamidino-2-phenylindole; association with constitutively heterochromatic foci; extent of binding of heterochromatin protein 1α; histone H3 methylation at lysine 9 and lysine 4; histone H4 lysine 8 acetylation; and replication timing within S-phase. Our results indicate that 4q35.2 does not resemble constitutive heterochromatin in FSHD or control myoblasts. Furthermore, in these analyses, the allelic 4q35.2 regions of FSHD myoblasts did not behave differently than those of control myoblasts. Other models for how D4Z4 array contraction causes long-distance regulation of gene expression incisneed to be tested.