{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:43:49Z","timestamp":1790779429146,"version":"4.1.0"},"reference-count":81,"publisher":"The Company of Biologists","issue":"10","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004097","name":"Fondation ARC pour la Recherche sur le Cancer","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004097","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004099","name":"Ligue Contre le Cancer","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004099","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100019973","name":"Minist\u00e8re de l'Enseignement Sup\u00e9rieur et de la Recherche","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100019973","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010463","name":"Institut Curie","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100010463","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>p53 (encoded by Trp53) is a tumor suppressor, but mouse models have revealed that increased p53 activity may cause bone marrow failure, likely through dimerization partner, RB-like, E2F4\/E2F5 and MuvB (DREAM) complex-mediated gene repression. Here, we designed a systematic approach to identify p53-DREAM pathway targets, the repression of which might contribute to abnormal hematopoiesis. We used Gene Ontology analysis to study transcriptomic changes associated with bone marrow cell differentiation, then chromatin immunoprecipitation-sequencing (ChIP-seq) data to identify DREAM-bound promoters. We next created positional frequency matrices to identify evolutionary conserved sequence elements potentially bound by DREAM. The same approach was developed to find p53-DREAM targets associated with brain abnormalities, also observed in mice with increased p53 activity. Putative DREAM-binding sites were found for 151 candidate target genes, of which 106 are mutated in a blood or brain genetic disorder. Twenty-one DREAM-binding sites were tested and found to impact gene expression in luciferase assays, to notably regulate genes mutated in dyskeratosis congenita (Rtel1), Fanconi anemia (Fanca), Diamond\u2013Blackfan anemia (Tsr2), primary microcephaly [Casc5 (or Knl1), Ncaph and Wdr62] and pontocerebellar hypoplasia (Toe1). These results provide clues on the role of the p53-DREAM pathway in regulating hematopoiesis and brain development, with implications for tumorigenesis.<\/jats:p>","DOI":"10.1242\/dmm.050376","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T03:45:12Z","timestamp":1693799112000},"source":"Crossref","is-referenced-by-count":14,"title":["A systematic approach identifies p53-DREAM pathway target genes associated with blood or brain abnormalities"],"prefix":"10.1242","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1218-4921","authenticated-orcid":false,"given":"Jeanne","family":"Rakotopare","sequence":"first","affiliation":[{"name":"Institut Curie 1 Genetics of Tumor Suppression , , Paris 75248 Cedex 05 , France"},{"name":"CNRS UMR3244 2 , Paris 75005, France"},{"name":"Sorbonne University 3 , Paris 75005, France"},{"name":"PSL Research University 4 , Paris 75005, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2797-1507","authenticated-orcid":false,"given":"Vincent","family":"Lejour","sequence":"additional","affiliation":[{"name":"Institut Curie 1 Genetics of Tumor Suppression , , Paris 75248 Cedex 05 , France"},{"name":"CNRS UMR3244 2 , Paris 75005, France"},{"name":"Sorbonne University 3 , Paris 75005, France"},{"name":"PSL Research University 4 , Paris 75005, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Duval","sequence":"additional","affiliation":[{"name":"Institut Curie 1 Genetics of Tumor Suppression , , Paris 75248 Cedex 05 , France"},{"name":"CNRS UMR3244 2 , Paris 75005, France"},{"name":"Sorbonne University 3 , Paris 75005, France"},{"name":"PSL Research University 4 , Paris 75005, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana","family":"Eldawra","sequence":"additional","affiliation":[{"name":"Institut Curie 1 Genetics of Tumor Suppression , , Paris 75248 Cedex 05 , France"},{"name":"CNRS UMR3244 2 , Paris 75005, France"},{"name":"Sorbonne University 3 , Paris 75005, France"},{"name":"PSL Research University 4 , Paris 75005, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugues","family":"Escoffier","sequence":"additional","affiliation":[{"name":"Paris-Saclay University 5 , \u00c9vry-Courcouronnes 91000 , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3798-4106","authenticated-orcid":false,"given":"Franck","family":"Toledo","sequence":"additional","affiliation":[{"name":"Institut Curie 1 Genetics of Tumor Suppression , , Paris 75248 Cedex 05 , France"},{"name":"CNRS UMR3244 2 , Paris 75005, France"},{"name":"Sorbonne University 3 , Paris 75005, France"},{"name":"PSL Research University 4 , Paris 75005, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2023,10,11]]},"reference":[{"key":"2023101807421266600_DMM050376C1","doi-asserted-by":"publisher","first-page":"2483","DOI":"10.1093\/bioinformatics\/bty127","article-title":"PWMScan: a fast tool for scanning entire genomes with a position-specific weight matrix","volume":"34","author":"Ambrosini","year":"2018","journal-title":"Bioinformatics"},{"key":"2023101807421266600_DMM050376C2","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1038\/s41467-022-28094-1","article-title":"The MuvB complex binds and stabilizes nucleosomes downstream of the transcription start site of cell-cycle dependent genes","volume":"13","author":"Asthana","year":"2022","journal-title":"Nat. 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