{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chen Z"],"funding":["Chongqing Science Fund","Chongqing Medical University","Doctor Research Project of Chongqing","National Natural Science Foundation of China","Chongqing Municipal Education Commission"],"pagination":["e20241248"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11748990"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["222(3)"],"pubmed_abstract":["Hematopoietic stem cells (HSCs) are susceptible to replication stress, which is a major contributor to HSC defects in Fanconi anemia (FA). Here, we report that HSCs relax the global chromatin by downregulating the expression of a chromatin architectural protein, DEK, in response to replication stress. DEK is abnormally accumulated in bone marrow (BM) CD34+ cells from patients with FA and in Fancd2-deficient HSCs. DEK haploinsufficiency promotes chromatin relaxation, replication stress relief, and function recovery of Fancd2-deficient HSCs. Furthermore, inhibition of DEK restores the proliferation of FA CD34+ cells in vitro and enhances their engraftment in vivo. Mechanistically, the activating transcription factor 2 (ATF2), specifically phosphorylated ATF2 at Thr69/71, was identified as a "],"journal":["The Journal of experimental medicine"],"pubmed_title":["Inhibition of DEK restores hematopoietic stem cell function in Fanconi anemia."],"pmcid":["PMC11748990"],"funding_grant_id":["82170115","CSTB2022BSXM-JCX0005","CSTB2022NSCQ-JQX0032","KJQN202400465","W0156","CSTB2023NSCQ-LZX0052"],"pubmed_authors":["Xie Y","Deng J","Wu F","Li L","Hou Y","Zhao X","Li Y","Chen Z","Xiao J","Lei Y","Zeng H","Gao S","Chen T"],"additional_accession":[]},"is_claimable":false,"name":"Inhibition of DEK restores hematopoietic stem cell function in Fanconi anemia.","description":"Hematopoietic stem cells (HSCs) are susceptible to replication stress, which is a major contributor to HSC defects in Fanconi anemia (FA). Here, we report that HSCs relax the global chromatin by downregulating the expression of a chromatin architectural protein, DEK, in response to replication stress. DEK is abnormally accumulated in bone marrow (BM) CD34+ cells from patients with FA and in Fancd2-deficient HSCs. DEK haploinsufficiency promotes chromatin relaxation, replication stress relief, and function recovery of Fancd2-deficient HSCs. Furthermore, inhibition of DEK restores the proliferation of FA CD34+ cells in vitro and enhances their engraftment in vivo. Mechanistically, the activating transcription factor 2 (ATF2), specifically phosphorylated ATF2 at Thr69/71, was identified as a ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Mar","modification":"2026-06-06T19:22:04.435Z","creation":"2026-06-04T03:12:48.069Z"},"accession":"S-EPMC11748990","cross_references":{"pubmed":["39836085"],"doi":["10.1084/jem.20241248"]}}