title: Olig2 is expressed late in human eosinophil development and controls Siglec-8 expression.
abstract: Oligodendrocyte transcription factor 2, a basic helix-loop-helix transcription factor that binds to E-box motifs, is known to have a key role in determining lineage specification of oligodendrocytes and motor neurons. In the present study, we report that oligodendrocyte transcription factor 2 is expressed in human eosinophils and involved in transcriptional activation of the gene encoding sialic acid binding immunoglobulin-like lectin 8 (Siglec-8), a late eosinophil-differentiation marker known to exert eosinophil apoptosis. When cord blood CD34+hematopoietic stem cells differentiated toward eosinophils during a 24-d culture period, oligodendrocyte transcription factor 2 protein was expressed in cord blood eosinophils on d 24, a time when cord blood eosinophils are considered fully differentiated, whereas it was not detectable on d 18 or at earlier time points. Oligodendrocyte transcription factor 2 protein was also abundantly expressed in human peripheral-blood eosinophils but not in neutrophils, monocytes, lymphocytes, or cord blood mast cells. RNA sequencing analysis showed that numerous genes, especially those encoding eosinophil surface molecules, were highly up-regulated along with OLIG2 Among the genes examined, SIGLEC-8 messenger RNA and protein were markedly down-regulated in parallel with OLIG2 by an oligodendrocyte transcription factor 2 small interfering RNA or a short hairpin RNA, as evidenced by real-time polymerase chain reaction, fluorescence-activated cell sorting, and Western blot analyses. In reporter gene and chromatin immunoprecipitation experiments, an E-box in the first intron was found to stimulate SIGLEC-8 gene transcription and to bind oligodendrocyte transcription factor 2. Hence, at least one important aspect of eosinophil differentiation is regulated by oligodendrocyte transcription factor 2, a transcription factor that has not previously been reported, to our knowledge, in normal granulocytes.
authors.affiliation: Department of Bionano Technology, Hanyang University, Ansan, Gyeonggi-do, Republic of Korea.
authors.forename: Sae Mi
authors.initials: SM
authors.lastname: Hwang
authors.affiliation: Department of Molecular and Life Sciences, Hanyang University, Ansan, Gyeonggi-do, Republic of Korea; and.
authors.forename: Tae Gi
authors.initials: TG
authors.lastname: Uhm
authors.affiliation: Department of Molecular and Life Sciences, Hanyang University, Ansan, Gyeonggi-do, Republic of Korea; and.
authors.forename: Seol Kyung
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Bionano Technology, Hanyang University, Ansan, Gyeonggi-do, Republic of Korea.
authors.forename: Su-Kang
authors.initials: SK
authors.lastname: Kong
authors.affiliation: Department of Molecular and Life Sciences, Hanyang University, Ansan, Gyeonggi-do, Republic of Korea; and.
authors.forename: Kyung Hwa
authors.initials: KH
authors.lastname: Jung
authors.affiliation: Department of Molecular and Life Sciences, Hanyang University, Ansan, Gyeonggi-do, Republic of Korea; and.
authors.forename: Bert
authors.initials: B
authors.lastname: Binas
authors.affiliation: Department of Bionano Technology, Hanyang University, Ansan, Gyeonggi-do, Republic of Korea; Department of Molecular and Life Sciences, Hanyang University, Ansan, Gyeonggi-do, Republic of Korea; and.
authors.forename: Young Gyu
authors.initials: YG
authors.lastname: Chai
authors.affiliation: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi-do, Republic of Korea.
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Park
authors.affiliation: Department of Bionano Technology, Hanyang University, Ansan, Gyeonggi-do, Republic of Korea; Department of Molecular and Life Sciences, Hanyang University, Ansan, Gyeonggi-do, Republic of Korea; and iychu@hanyang.ac.kr.
authors.forename: Il Yup
authors.initials: IY
authors.lastname: Chung
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis* / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D024721:E-Box Elements / Q000235:genetics; D004804:Eosinophils / Q000166:cytology* / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood; D007438:Introns / Q000235:genetics; D037102:Lectins / Q000096:biosynthesis* / Q000235:genetics; D008407:Mast Cells / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D038042:Myelopoiesis / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009504:Neutrophils / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D017423:Sequence Analysis, RNA
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D051792:Basic Helix-Loop-Helix Proteins; D037102:Lectins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C405708:OLIG2 protein, human; C403967:SIGLEC8 protein, human
keywords: MBP; MMP25; RNA-seq; cord blood; eosinophil