Dalal Yamini
Chromatin Structure and Epigenetic Mechanisms Unit, Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Biochem Cell Biol. 2009 Feb;87(1):273-82. doi: 10.1139/O08-135.
Centromeres are the discrete sites of spindle microtubule attachment on chromosomes during mitosis and meiosis in all eukaryotes. These highly specialized chromatin structures typically occupy the same site for thousands of generations, yet the mechanism by which centromeres are established, maintained, and function remain a mystery. In metazoans, centromeric DNA sequence has proven not to be the key determinant of centromeric identity; therefore, centromeres are thought to be epigenetically specified by their specialized chromatin structure. In all eukaryotes, the centromere-specific histone H3 variant CenH3 replaces canonical H3 within nucleosomes at centric chromatin. This specialized nucleosome is the building block upon which all other centromere-associated proteins depend. This review highlights exciting new findings that have resulted in a paradigm shift in our understanding of CenH3 assembly into centromeric chromatin, CenH3 nucleosomal structure, CenH3 chromatin folding, the contribution of these factors to centromeric identity, and finally, the intimate role cell-cycle-regulated transcription and pericentric heterochromatin play in the maintenance and integrity of centromeres.
在所有真核生物的有丝分裂和减数分裂过程中，着丝粒是纺锤体微管附着于染色体的离散位点。这些高度特化的染色质结构通常在数千代中占据相同的位点，然而着丝粒的建立、维持和功能机制仍然是个谜。在后生动物中，着丝粒DNA序列已被证明不是着丝粒身份的关键决定因素；因此，着丝粒被认为是由其特化的染色质结构在表观遗传上指定的。在所有真核生物中，着丝粒特异性组蛋白H3变体CenH3在着丝粒染色质的核小体中取代了经典的H3。这种特化的核小体是所有其他着丝粒相关蛋白所依赖的构建块。本综述重点介绍了一些令人兴奋的新发现，这些发现导致我们在理解CenH3组装进入着丝粒染色质、CenH3核小体结构、CenH3染色质折叠、这些因素对着丝粒身份的贡献，以及最后，细胞周期调控转录和着丝粒周围异染色质在着丝粒的维持和完整性中所起的密切作用方面发生了范式转变。
