SHREC Complex Regulates The Substitution Of H3 And Cnp1 Nucleosomes By Acetylation Within Centromere

Correct assembly of centromeres is one of the basic requirements for cell division.CENP-A / Cnp1 nucleosomes located specifically in the centromere core region are the basis for kinetochore assembly and play a key role in chromosome segregation during mitosis and meiosis.In this project,we used a genetic screening system in Schizosaccharomyces pombe to find the genes involved in centromere assembly,and revealed a new mechanism for quantitative regulation of CENP-A /Cnp1 nucleosome incorporation in centromere.Previous studies have shown that the MBF transcription factor complex regulates the level of of CENP-A / Cnp1 nucleosome incorporation through modulating cnp1 transcription level.In this study,we found that:(1)besides transcriptional regulation,Dnajc9 regulates the localization of Cnp1 nucleosome and plays an important role in maintaining the boundaries between the Cnp1-domain/central region and the pericentromeric heterochromatin regions.The SHREC complex – containing Clr1,Clr2,and Clr3-also affects the localization of Cnp1 nucleosome at a non-transcriptional level,and its mechanism is different from that of Dnajc9.(2)The deacetylation function of the HDAC module in SHREC reverses the localization of Cnp1 nucleosome.This function may specifically target the centromere central region via Clr2,in which the D10 site of Clr2 plays an important role.(3)Acetylation of H3K14 in the centromeric region supports H3 expulsion and helps Cnp1 nucleosome incorporation into the centromeric core region.However,not all H3K14ac-related proteins,such as Sir2,act on centromeric core region to regulate the localization of Cnp1.In summary,we have found two relatively independent factors that regulate the localization of CENP-A / Cnp1 in the chromatin assembly level.Combined with previous work,these results suggest that centromere assembly is regulated by various factors at multiple levels.