RT Journal Article
SR Electronic
T1 ATAD2 controls chromatin-bound HIRA turnover
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101151
DO 10.26508/lsa.202101151
VO 4
IS 12
A1 Tao Wang
A1 Daniel Perazza
A1 Fayçal Boussouar
A1 Matteo Cattaneo
A1 Alexandre Bougdour
A1 Florent Chuffart
A1 Sophie Barral
A1 Alexandra Vargas
A1 Ariadni Liakopoulou
A1 Denis Puthier
A1 Lisa Bargier
A1 Yuichi Morozumi
A1 Mahya Jamshidikia
A1 Isabel Garcia-Saez
A1 Carlo Petosa
A1 Sophie Rousseaux
A1 André Verdel
A1 Saadi Khochbin
YR 2021
UL https://www.life-science-alliance.org/content/4/12/e202101151.abstract
AB 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.