TY - JOUR T1 - ATAD2 controls chromatin-bound HIRA turnover JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202101151 VL - 4 IS - 12 SP - e202101151 AU - Tao Wang AU - Daniel Perazza AU - Fayçal Boussouar AU - Matteo Cattaneo AU - Alexandre Bougdour AU - Florent Chuffart AU - Sophie Barral AU - Alexandra Vargas AU - Ariadni Liakopoulou AU - Denis Puthier AU - Lisa Bargier AU - Yuichi Morozumi AU - Mahya Jamshidikia AU - Isabel Garcia-Saez AU - Carlo Petosa AU - Sophie Rousseaux AU - André Verdel AU - Saadi Khochbin Y1 - 2021/12/01 UR - https://www.life-science-alliance.org/content/4/12/e202101151.abstract N2 - Taking advantage of the evolutionary conserved nature of ATAD2, we report here a series of parallel functional studies in human, mouse, and Schizosaccharomyces pombe to investigate ATAD2’s conserved functions. In S. pombe, the deletion of ATAD2 ortholog, abo1, leads to a dramatic decrease in cell growth, with the appearance of suppressor clones recovering normal growth. The identification of the corresponding suppressor mutations revealed a strong genetic interaction between Abo1 and the histone chaperone HIRA. In human cancer cell lines and in mouse embryonic stem cells, we observed that the KO of ATAD2 leads to an accumulation of HIRA. A ChIP-seq mapping of nucleosome-bound HIRA and FACT in Atad2 KO mouse ES cells demonstrated that both chaperones are trapped on nucleosomes at the transcription start sites of active genes, resulting in the abnormal presence of a chaperone-bound nucleosome on the TSS-associated nucleosome-free regions. Overall, these data highlight an important layer of regulation of chromatin dynamics ensuring the turnover of histone-bound chaperones. ER -