Journal
GENES & DEVELOPMENT
Volume 29, Issue 10, Pages 1058-1073Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.259432.115
Keywords
RG loop; CENP-A; higher-order chromatin structure; CENP-N; chromosome congression; cell cycle
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Funding
- National Natural Science Foundation of China [91219202, 31471218, 31210103914]
- Ministry of Science and Technology of China [2015CB856200, 2011CB966300]
- Chinese Academy of Sciences (CAS) Strategic Priority Research Program [XDA01010304]
- Key Research Program [KJZD-EW-L05]
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Specific recognition of centromere-specific histone variant CENP-A-containing chromatin by CENP-N is an essential process in the assembly of the kinetochore complex at centromeres prior to mammalian cell division. However, the mechanisms of CENP-N recruitment to centromeres/kinetochores remain unknown. Here, we show that a CENP-A-specific RG loop (Arg80/Gly81) plays an essential and dual regulatory role in this process. The RG loop assists the formation of a compact ladder-like structure of CENP-A chromatin, concealing the loop and thus impairing its role in recruiting CENP-N. Upon G1/S-phase transition, however, centromeric chromatin switches from the compact to an open state, enabling the now exposed RG loop to recruit CENP-N prior to cell division. Our results provide the first insights into the mechanisms by which the recruitment of CENP-N is regulated by the structural transitions between compaction and relaxation of centromeric chromatin during the cell cycle.
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