title: ELL inhibits E2F1 transcriptional activity by enhancing E2F1 deacetylation via recruitment of histone deacetylase 1.
abstract: ELL (eleven-nineteen lysine-rich leukemia protein) was first identified as a translocation partner of MLL in acute myeloid leukemia; however, the exact mechanism of its action has remained elusive. In this study, we identified ELL as a direct downstream target gene of E2F1. Coimmunoprecipitation assays showed that ELL interacted with E2F1 in vitro and in vivo, leading to inhibition of E2F1 transcriptional activity. In addition, ELL enhanced E2F1 deacetylation via recruitment of histone deacetylase 1 (HDAC1). Notably, the MLL-ELL fusion protein lost the inhibitory role of ELL in E2F1 transcriptional activity. Furthermore, DNA damage induced ELL in an E2F1-dependent manner and ELL protected cells against E2F1-dependent apoptosis. Our findings not only connect ELL to E2F1 function and uncover a novel role of ELL in response to DNA damage but also provide an insight into the mechanism for MLL-ELL-associated leukemogenesis.
authors.affiliation: The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Ji
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Ouyang
authors.forename: Wuhan
authors.initials: W
authors.lastname: Xiao
mesh_terms: D000818:Animals; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011519:Proto-Oncogenes / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors / Q000378:metabolism*; D014178:Translocation, Genetic / Q000235:genetics / Q000502:physiology
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C090862:ELL protein, human; D035602:Transcriptional Elongation Factors; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1