title: The up-regulation of miR-199b-5p in erythroid differentiation is associated with GATA-1 and NF-E2.
abstract: MicroRNAs (miRNAs) represent a class of small non-coding regulatory RNAs that play important roles in normal hematopoiesis, including erythropoiesis. Although studies have identified several miRNAs that regulate erythroid commitment and differentiation, we do not understand the mechanism by which the crucial erythroid transcription factors, GATA-1and NF-E2 directly regulate and control differentiation via miRNA pathways. In this study, we identified miR-199b-5p as a key regulator of human erythropoiesis, and its expression was up-regulated during the erythroid differentiation of K562 cells. Furthermore, the increase of miR-199b-5p in erythroid cells occurred in a GATA-1- and NF-E2-dependent manner during erythrocyte maturation. Both GATA-1 and NF-E2 bound upstream of the miR-199b gene locus and activated its transcription. Forced expression of miRNA-199b-5p in K562 cells affected erythroid cell proliferation and maturation. Moreover, we identified c-Kit as a direct target of miR-199b-5p in erythroid cells. Taken together, our results establish a functional link among the erythroid transcription factors GATA-1/NF-E2, miR-199b-5p and c-Kit, and provide new insights into the coupling of transcription and post-transcription regulation in erythroid differentiation.
authors.affiliation: Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), National Laboratory of Medical Molecular Biology, Beijing 100005, People's Republic of China ; Institute of Molecular Medicine, Medical School, Henan University, KaiFeng, 475000, People's Republic of China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Bai
authors.forename: Zhongzu
authors.initials: Z
authors.lastname: Zhang
authors.forename: Weihua
authors.initials: W
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
authors.forename: Xueju
authors.initials: X
authors.lastname: Wei
authors.forename: Yanni
authors.initials: Y
authors.lastname: Ma
authors.forename: Junwu
authors.initials: J
authors.lastname: Zhang
authors.forename: Jia
authors.initials: J
authors.lastname: Yu
authors.forename: Guotao
authors.initials: G
authors.lastname: Sun
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation; D041905:Erythroid Cells / Q000378:metabolism*; D004920:Erythropoiesis; D050982:GATA1 Transcription Factor / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D050984:NF-E2 Transcription Factor, p45 Subunit / Q000235:genetics / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D035683:MicroRNAs; D050984:NF-E2 Transcription Factor, p45 Subunit; C494692:NFE2 protein, human; C531408:mirn199 microRNA, human; D019009:Proto-Oncogene Proteins c-kit