FBSコロキウム 245回染色体生物学研究室

高等動物セントロメアのエピジェネティック制御

The centromere is an essential genome region where the kinetochore is established for faithful chromosome segregation. In most organisms, centromeres are specified by sequence-independent epigenetic mechanisms through the deposition of histone H3-variant CENP-A into chromatin. Therefore, it is critical to know how CENP-A is deposited into centromeric chromatin. We previously showed that the chicken Mis18 complex directly binds to the CENP-A nucleosome and is recognized by the pre-deposition CENP-A-H4-HJURP (CENP-A specific chaperon) complex for new CENP-A incorporation. However, it is still unknown how the pre-deposition CENP-A-H4-HJURP complex correctly transfers the CENP-A into centromeric chromatin and how the CENP-A nucleosome triggers to assemble the kinetochore in the vertebrate cells. Here, we analyzed various CENP-A domains in the chicken DT40 cells, using a gene complementation assay. We found that while both N- and C-terminal tails of CENP-A were dispensable, the alpha-1 helix region near CATD (CENP-A targeting domain) was essential for CENP-A deposition and centromere maintenance in chicken DT40 cells, which is not the case for human CENP-A. Combined biochemical data, we propose that the essentiality of CENP-A depends on its binding mode to HJURP, which is variable during evolution.