title: PU.1 affects proliferation of the human acute myeloid leukemia U937 cell line by directly regulating MEIS1.
abstract: The transcription factor PU.1 is a member of the ETS family, which is expressed in a wide variety of hematopoietic lineages. Accumulating evidence has indicated that PU.1 plays a key role in hematopoiesis, and reduced expression of PU.1 leads to the pathogenesis of human myeloid leukemia. As a multi-functional factor, PU.1 is also required for mixed lineage leukemia (MLL) stem cell potential and the development of MLL. However, the function of PU.1 in human non-MLL leukemia and its molecular mechanism remains poorly understood. In the present study, PU.1 siRNA was demonstrated to efficiently inhibit the transcription level of oncogene MEIS1 in the human acute myeloid non-MLL leukemia U937 cell line. In addition, PU.1, as a positive regulator of MEIS1, performed a crucial role in maintaining cell proliferation. Using electrophoretic mobility shift assay, chromatin immunoprecipitation analysis and luciferase reporter assay, previously unexplored evidence that PU.1 activated the MEIS1 promoter through a conserved binding motif in vitro and in vivo was further defined. Overall, the present study provides insight into the molecular mechanism of the contribution of PU.1 to the pathogenesis of non-MLL U937 cells, which is mediated by direct regulation of MEIS1 transcription. The present data reveal the possibility of developing an alternative therapy for non-MLL leukemia by targeting PU.1-mediated MEIS1 gene activation.
authors.affiliation: Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, P.R. China ; Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, MA 02142, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Chemistry, University of Massachusetts Boston, Boston, MA 02125, USA.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, MA 02142, USA ; Department of Prosthodontics, Ninth People's Hospital, College of Stomatology, School of Medicine, Shanghai Jiao Tong University, Shanghai Key Laboratory of Stomatology, Shanghai 200011, P.R. China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Respiratory Department, 2nd Branch of First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Guan
keywords: MEIS1; PU.1; leukemia; transcription