RT Journal Article
SR Electronic
T1 Ccq1–Raf2 interaction mediates CLRC recruitment to establish heterochromatin at telomeres
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101106
DO 10.26508/lsa.202101106
VO 4
IS 11
A1 Shaohua Shi
A1 Yuanze Zhou
A1 Yanjia Lu
A1 Hong Sun
A1 Jing Xue
A1 Zhenfang Wu
A1 Ming Lei
YR 2021
UL https://www.life-science-alliance.org/content/4/11/e202101106.abstract
AB Telomeres, highly ordered DNA-protein complexes at eukaryotic linear chromosome ends, are specialized heterochromatin loci conserved among eukaryotes. In Schizosaccharomyces pombe, the shelterin complex is important for subtelomeric heterochromatin establishment. Despite shelterin has been demonstrated to mediate the recruitment of the Snf2/histone deacetylase–containing repressor complex (SHREC) and the Clr4 methyltransferase complex (CLRC) to telomeres, the mechanism involved in telomeric heterochromatin assembly remains elusive due to the multiple functions of the shelterin complex. Here, we found that CLRC plays a dominant role in heterochromatin establishment at telomeres. In addition, we identified a series of amino acids in the shelterin subunit Ccq1 that are important for the specific interaction between Ccq1 and the CLRC subunit Raf2. Finally, we demonstrated that the Ccq1–Raf2 interaction is essential for the recruitment of CLRC to telomeres, that contributes to histone H3 lysine 9 methylation, nucleosome stability and the shelterin-chromatin association, promoting a positive feedback mechanism for the nucleation and spreading of heterochromatin at subtelomeres. Together, our findings provide a mechanistic understanding of subtelomeric heterochromatin assembly by shelterin-dependent CLRC recruitment to chromosomal ends.