Comparison of TFII-I gene family members deleted in Williams-Beuren syndrome
Comparison of TFII-I gene family members deleted in Williams-Beuren syndrome
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DOI：
10.1110/ps.04747604
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发表时间：
2004-10-01
期刊：
影响因子：
8
通讯作者：
Tassabehji, M
中科院分区：
文献类型：
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作者：
Hinsley, TA;Cunliffe, P;Tassabehji, M
Williams-Beuren 综合征 (WBS) 是一种由 7q11.23 处的微缺失（通常大小为 1.5 兆碱基）引起的神经系统疾病。非典型患者暗示这种多基因缺失端粒末端的基因是 WBS 病理学的主要候选者，特别是与该病症相关的不平等认知特征。我们最近发现了一个基因 (GTF2IRD2)，它与位于关键端粒区域的独特转录因子家族（TFII-I 家族）的其他成员具有同源性。这项研究利用生物信息学工具，重点对该基因家族进行详细评估，重点关注其特征结构成分，如亮氨酸拉链 (LZ) 和 I-重复元件，试图识别有助于功能预测的特征。系统发育分析确定了家族成员之间共享的不同 I 重复进化枝。将功能数据与此类进化枝联系起来表明它们与 DNA 结合有关。所有家族成员共有的 PEST、协同控制基序和 sumoylation 位点的鉴定表明调节这些因子的稳定性和转录活性的共享机制。此外，每个 TFII-I 家族成员的短截短亚型的识别/分离意味着一种自我调节模式。 GTF21 和 GTF2IRD2 之间具有极高的同一性，表明异二聚体和同二聚体都是可能的，并表明它们各自的短亚型之间存在重叠功能。 GTF2I 和 GTF2IRD2 短亚型之间的这种交叉反应可能是 7q11.23 染色体重排的进化驱动力，而小鼠同线区域中不存在这种重排。
Williams-Beuren syndrome (WBS) is a neurological disorder resulting from a microdeletion, typically 1.5 megabases in size, at 7q11.23. Atypical patients implicate genes at the telomeric end of this multigene deletion as the main candidates for the pathology of WBS in particular the unequal cognitive profile associated with the condition. We recently identified a gene (GTF2IRD2) that shares homology with other members of a unique family of transcription factors (TFII-I family), which reside in the critical telomeric region. Using bioinformatics tools this study focuses on the detailed assessment of this gene family, concentrating on their characteristic structural components such as the leucine zipper (LZ) and I-repeat elements, in an attempt to identify features that could aid functional predictions. Phylogenetic analysis identified distinct I-repeat clades shared between family members. Linking functional data to one such clade has implicated them in DNA binding. The identification of PEST, synergy control motifs, and sumoylation sites common to all family members suggest a shared mechanism regulating the stability and transcriptional activity of these factors. In addition, the identification/isolation of short truncated isoforms for each TFII-I family member implies a mode of self-regulation. The exceptionally high identity shared between GTF21 and GTF2IRD2, suggests that heterodimers as well as homodimers are possible, and indicates overlapping functions between their respective short isoforms. Such cross-reactivity between GTF2I and GTF2IRD2 short isoforms might have been the evolutionary driving force for the 7q11.23 chromosomal rearrangement not present in the syntenic region in mice.