Altered replication timing of the HIRA/Tuple1 locus in the DiGeorge and Velocardiofacial syndromes
Altered replication timing of the HIRA/Tuple1 locus in the DiGeorge and Velocardiofacial syndromes
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DOI：
10.1016/j.gene.2004.02.029
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发表时间：
2004-05-26
期刊：
影响因子：
3.5
通讯作者：
Saccone, S
中科院分区：
文献类型：
--
作者：
D'Antoni, S;Mattina, T;Saccone, S
DiGeorge和Velocardiofacial综合征（DGSNCFS）具有相似的复杂表型，包括心血管、颅面和胸腺畸形，并与22 q11染色体带的杂合缺失相关。22q11.21子带中的典型缺失区（这里称为TDR 22）是非常基因密集的，并且在几项研究中已经精确地定义了缺失的程度。然而，迄今为止，没有证据表明单倍不足的机制，可以完全解释DGSNCFS表型。在这项研究中，我们表明，候选基因HIRA/Tuple 1映射非缺失的TDR 22，在DGSNCFS受试者提出了一个延迟的复制时间。此外，我们观察到的细胞比例增加，显示HIRA/Tuple 1基因座定位于核周边。已知复制时间和核位置通常与相关DNA区域的转录活性相关。我们认为，非缺失的TDR 22的复制/核定位模式的改变表明基因调节的改变，因此DGS/VCFS中的转线粒体发生了改变。(C)2004 Elsevier B. V.保留所有权利。
DiGeorge and Velocardiofacial syndromes (DGSNCFS) are endowed by a similar complex phenotype including cardiovascular, craniofacial, and thymic malformations, and are associated with heterozygous deletions of 22q11 chromosomal band. The Typically Deleted Region in the 22q11.21 subband (here called TDR22) is very gene-dense, and the extent of the deletion has been defined precisely in several studies. However, to date there is no evidence for a mechanism of haploinsufficiency that can fully explain the DGSNCFS phenotype. In this study, we show that the candidate gene HIRA/Tuple1 mapping on the non-deleted TDR22, in DGSNCFS subjects presents a delayed replication timing. Moreover, we observed an increase in the cell ratio showing the HIRA/Tuple1 locus localised toward the nuclear periphery. It is known that replication timing and nuclear location are generally correlated to the transcription activity of the relative DNA region. We propose that the alteration in the replication/nuclear location pattern of the non-deleted TDR22 indicates an altered gene regulation hence an altered transcritpion in DGS/VCFS. (C) 2004 Elsevier B.V. All rights reserved.