Chimge Nyam-Osor, Makeyev Aleksandr V, Ruddle Frank H, Bayarsaihan Dashzeveg
Department of Molecular, Cellular, and Craniofacial Biology, Birth Defects Center, University of Louisville, 501 South Preston Street, Louisville, KY 40292, USA.
Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):9006-10. doi: 10.1073/pnas.0803051105. Epub 2008 Jun 25.
GTF2I and GTF2IRD1 encode members of the TFII-I transcription factor family and are prime candidates in the Williams syndrome, a complex neurodevelopmental disorder. Our previous expression microarray studies implicated TFII-I proteins in the regulation of a number of genes critical in various aspects of cell physiology. Here, we combined bioinformatics and microarray results to identify TFII-I downstream targets in the vertebrate genome. These results were validated by chromatin immunoprecipitation and siRNA analysis. The collected evidence revealed the complexity of TFII-I-mediated processes that involve distinct regulatory networks. Altogether, these results lead to a better understanding of specific molecular events, some of which may be responsible for the Williams syndrome phenotype.
GTF2I和GTF2IRD1编码TFII-I转录因子家族成员,是威廉姆斯综合征(一种复杂的神经发育障碍)的主要候选基因。我们之前的表达微阵列研究表明,TFII-I蛋白参与调控许多在细胞生理学各个方面至关重要的基因。在这里,我们结合生物信息学和微阵列结果,以识别脊椎动物基因组中TFII-I的下游靶点。这些结果通过染色质免疫沉淀和小干扰RNA分析得到了验证。收集到的证据揭示了TFII-I介导的过程的复杂性,这些过程涉及不同的调控网络。总之,这些结果有助于更好地理解特定的分子事件,其中一些可能与威廉姆斯综合征的表型有关。