DNaseI hypersensitivity at gene-poor, FSH dystrophy-linked 4q35.2.
DNaseI hypersensitivity at gene-poor, FSH dystrophy-linked 4q35.2.
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DOI：
10.1093/nar/gkp833
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发表时间：
2009-12
影响因子：
14.9
通讯作者：
Ehrlich M
中科院分区：
文献类型：
--
作者：
Xu X;Tsumagari K;Sowden J;Tawil R;Boyle AP;Song L;Furey TS;Crawford GE;Ehrlich M
一个亚端粒区，4q35.2，涉及面肩肱型肌营养不良症（FSHD），一种显性疾病，认为涉及局部染色质的致病性变化。FSHD患者在4q35.2处的串联3.3-kb重复（D4 Z4）拷贝太少。没有表型与在10q26.3处具有几乎相同的重复的几个拷贝相关。标准的表达分析没有给出有关基因的明确答案。为了研究短D4 Z4阵列对非常缺乏基因的4q35.2基因表达的致病作用，并找到转录控制、未注释基因和染色质结构的染色质标志，我们绘制了FSHD和对照成肌细胞中的DNaseI超敏感（DH）位点。使用定制的平铺阵列（DNA酶芯片），我们发现了出乎意料的两个大的基因沙漠在这个4-Mb区域的DH位点。一个位点优先见于FSHD成肌细胞。其他几个被定位为>0.7 Mb，来自已知在肌肉谱系中有活性的基因，并且也在培养的成纤维细胞中观察到，但不在淋巴细胞、骨髓细胞或肝细胞中观察到。它们在中胚层细胞中的选择性出现表明了功能性。我们的研究结果表明，4q35.2的基因沙漠地区可能有功能的意义，也可能FSHD，尽管他们缺乏已知的基因。
A subtelomeric region, 4q35.2, is implicated in facioscapulohumeral muscular dystrophy (FSHD), a dominant disease thought to involve local pathogenic changes in chromatin. FSHD patients have too few copies of a tandem 3.3-kb repeat (D4Z4) at 4q35.2. No phenotype is associated with having few copies of an almost identical repeat at 10q26.3. Standard expression analyses have not given definitive answers as to the genes involved. To investigate the pathogenic effects of short D4Z4 arrays on gene expression in the very gene-poor 4q35.2 and to find chromatin landmarks there for transcription control, unannotated genes and chromatin structure, we mapped DNaseI-hypersensitive (DH) sites in FSHD and control myoblasts. Using custom tiling arrays (DNase-chip), we found unexpectedly many DH sites in the two large gene deserts in this 4-Mb region. One site was seen preferentially in FSHD myoblasts. Several others were mapped >0.7 Mb from genes known to be active in the muscle lineage and were also observed in cultured fibroblasts, but not in lymphoid, myeloid or hepatic cells. Their selective occurrence in cells derived from mesoderm suggests functionality. Our findings indicate that the gene desert regions of 4q35.2 may have functional significance, possibly also to FSHD, despite their paucity of known genes.
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DOI：
10.1083/jcb.200508121
发表时间：
2006-05-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hou R;Liu L;Anees S;Hiroyasu S;Sibinga NE
通讯作者：
Sibinga NE
影响因子：
4.6
作者：
Jeong, YS;El-Jaick, K;Epstein, DJ
通讯作者：
Epstein, DJ
影响因子：
7
作者：
Costantini, M;Clay, O;Bernardi, G
通讯作者：
Bernardi, G
影响因子：
64.8
作者：
Gabellini, D;D'Antona, G;Tupler, R
通讯作者：
Tupler, R
影响因子：
64.8
作者：
Guelen, Lars;Pagie, Ludo;van Steensel, Bas
通讯作者：
van Steensel, Bas