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ATAD2 controls chromatin-bound HIRA turnover
- Source :
- Life Science Alliance, Life Science Alliance, 2021, ⟨10.26508/lsa.202101151⟩, Life Science Alliance, Life Science Alliance LLC, 2021, ⟨10.26508/lsa.202101151⟩
- Publication Year :
- 2021
- Publisher :
- Life Science Alliance LLC, 2021.
-
Abstract
- Parallel study of multiple model systems points to the evolutionary conserved protein ATAD2, as a critical histone chaperone auxiliary factor.<br />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.
- Subjects :
- Genotype
Cell Cycle Proteins
[SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology
Transfection
Gene Knockout Techniques
Mice
Schizosaccharomyces
Animals
Humans
Histone Chaperones
Research Articles
Cell Proliferation
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology
Mouse Embryonic Stem Cells
Hep G2 Cells
Nucleosomes
DNA-Binding Proteins
ATPases Associated with Diverse Cellular Activities
Schizosaccharomyces pombe Proteins
Microorganisms, Genetically-Modified
Gene Deletion
Research Article
HeLa Cells
Signal Transduction
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 25751077
- Volume :
- 4
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Life Science Alliance
- Accession number :
- edsair.pmid.dedup....c9bfdf8371beb8cb4f1b2da0f414c032