Role of CHD1 in Chromatin Remodeling and Transcriptional Regulation

9604154蛋白质chd1与延长的(去压缩的)间期染色质的转录活性区域有关。这种蛋白质的结构特征在漫长的进化过程中得到了保存，这表明它在酵母、苍蝇和哺乳动物等各种生物中发挥着类似的功能。这些特征包括一个染色域，它与HP1和Polycomb等蛋白质有关；一个ATPase/解旋酶结构域，它与SNF2/SWI2和Brahma等蛋白质有关；以及一个DNA结合域，它与A(富含T的DNA)的小沟特异相互作用。本研究旨在深入了解CHD1及其相关蛋白在染色质结构重塑和基因表达调控中所起的作用。在用果蝇进行的实验中，已经确定了几个CHD1活性的目标基因，这些实验将包括：(I)对处于不同发育和生理状态的果蝇的多线染色体进行免疫细胞化学定位研究；(Ii)CHD1标志域直接突变的后果的遗传学研究；(Iii)确定与CHD1相互作用的目标基因的特定区域；以及(Iv)CHD1突变体以及这些突变的增强剂和/或抑制物的遗传筛选。这项研究应该会对基因调控的知识做出实质性的贡献。特别是，它应该有助于阐明染色质结构的改变决定转录装置的可及性的机制。%CHD1蛋白与延长的(去压缩的)间期染色质的转录活性区域有关。这种蛋白质的结构特征在漫长的进化过程中得到了保存，这表明它在酵母、苍蝇和哺乳动物等各种生物中发挥着类似的功能。本研究旨在深入了解CHD1及其相关蛋白在染色质结构重塑和基因表达调控中的作用。特别是，它应该有助于阐明染色质结构的改变决定转录装置的可及性的机制。***

9604154 Perry The protein CHD1 is associated with transcriptionally active regions of extended (decompacted) interphase chromatin. The structural features of this protein have been preserved over a long period of evolution, suggesting that it performs analogous functions in organisms as diverse as yeast, flies and mammals. These features include a chromo domain, relating it to proteins like HP1 and Polycomb; an ATPase/helicase domain, relating it to proteins like SNF2/SWI2 and Brahma; and a DNA-binding domain that specifically interacts with the minor groove of A(T-rich DNA. This research is aimed at gaining deeper insight into the roles played by CHD1 and its associated proteins in the remodeling of chromatin structure and the regulation of gene expression. Experiments with Drosophila, in which several target genes of CHD1 activity have been identified, will include (i) immunocytochemical localization studies of polytene chromosomes from flies in different developmental and physiological states; (ii) genetic studies of the consequences of directed mutations in the signature domains of CHD1; (iii) determination of the particular regions of target genes that interact with CHD1; and (iv) a genetic screen for CHD1 mutants and for enhancers and/or suppressors of these mutations. This research should contribute substantially to the knowledge of gene regulation. In particular, it should help illuminate mechanisms by which modifications of chromatin structure determine accessibility to the transcriptional apparatus. %%% The protein CHD1 is associated with transcriptionally active regions of extended (decompacted) interphase chromatin. The structural features of this protein have been preserved over a long period of evolution, suggesting that it performs analogous functions in organisms as diverse as yeast, flies and mammals. This research is aimed at gaining deeper insight into the roles played by CHD1 and its associated proteins in the remodeling of chromatin structure and the regulation o f gene expression. In particular, it should help illuminate mechanisms by which modifications of chromatin structure determine accessibility to the transcriptional apparatus. ***