title: mll ortholog containing functional domains of human MLL is expressed throughout the zebrafish lifespan and in haematopoietic tissues.
abstract: Infant leukaemia is an embryonal disease in which the underlying MLL translocations initiate in utero. Zebrafish offer unique potential to understand how MLL impacts haematopoiesis from the earliest embryonic timepoints and how translocations cause leukaemia as an embryonal process. In this study, a zebrafish mll cDNA syntenic to human MLL spanning the 5' to 3' UTRs, was cloned from embryos, and mll expression was characterized over the zebrafish lifespan. The protein encoded by the 35-exon ORF exhibited 46·4% overall identity to human MLL and 68-100% conservation in functional domains (AT-hooks, SNL, CXXC, PHD, bromodomain, FYRN, taspase1 sites, FYRC, SET). Maternally supplied transcripts were detected at 0-2 hpf. Strong ubiquitous early zygotic expression progressed to a cephalo-caudal gradient during later embryogenesis. mll was expressed in the intermediate cell mass (ICM) where primitive erythrocytes are produced and in the kidney where definitive haematopoiesis occurs in adults. mll exhibits high cross species conservation, is developmentally regulated in haematopoietic and other tissues and is expressed from the earliest embryonic timepoints throughout the zebrafish lifespan. Haematopoietic tissue expression validates using zebrafish for MLL haematopoiesis and leukaemia models.
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Blaine W
authors.initials: BW
authors.lastname: Robinson
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Germano
authors.forename: Yuanquan
authors.initials: Y
authors.lastname: Song
authors.forename: Joshua
authors.initials: J
authors.lastname: Abrams
authors.forename: Marion
authors.initials: M
authors.lastname: Scott
authors.forename: Ilaria
authors.initials: I
authors.lastname: Guariento
authors.forename: Natascia
authors.initials: N
authors.lastname: Tiso
authors.forename: Francesco
authors.initials: F
authors.lastname: Argenton
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rhodes
authors.forename: John P
authors.initials: JP
authors.lastname: Kanki
authors.forename: A Thomas
authors.initials: AT
authors.lastname: Look
authors.forename: Rita J
authors.initials: RJ
authors.lastname: Balice-Gordon
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Felix
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019295:Computational Biology; D018076:DNA, Complementary / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000502:physiology; D006413:Hematopoietic System / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics / Q000378:metabolism*; D016366:Open Reading Frames; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013045:Species Specificity; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger; D051788:Myeloid-Lymphoid Leukemia Protein