title: Identification of neural crest and glial enhancers at the mouse Sox10 locus through transgenesis in zebrafish.
abstract: Sox10 is a dynamically regulated transcription factor gene that is essential for the development of neural crest-derived and oligodendroglial populations. Developmental genes often require multiple regulatory sequences that integrate discrete and overlapping functions to coordinate their expression. To identify Sox10 cis-regulatory elements, we integrated multiple model systems, including cell-based screens and transposon-mediated transgensis in zebrafish, to scrutinize mammalian conserved, noncoding genomic segments at the mouse Sox10 locus. We demonstrate that eight of 11 Sox10 genomic elements direct reporter gene expression in transgenic zebrafish similar to patterns observed in transgenic mice, despite an absence of observable sequence conservation between mice and zebrafish. Multiple segments direct expression in overlapping populations of neural crest derivatives and glial cells, ranging from pan-Sox10 and pan-neural crest regulatory control to the modulation of expression in subpopulations of Sox10-expressing cells, including developing melanocytes and Schwann cells. Several sequences demonstrate overlapping spatial control, yet direct expression in incompletely overlapping developmental intervals. We were able to partially explain neural crest expression patterns by the presence of head to head SoxE family binding sites within two of the elements. Moreover, we were able to use this transcription factor binding site signature to identify the corresponding zebrafish enhancers in the absence of overall sequence homology. We demonstrate the utility of zebrafish transgenesis as a high-fidelity surrogate in the dissection of mammalian gene regulation, especially those with dynamically controlled developmental expression.
authors.affiliation: Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Anthony
authors.initials: A
authors.lastname: Antonellis
authors.forename: Jimmy L
authors.initials: JL
authors.lastname: Huynh
authors.forename: Shih-Queen
authors.initials: SQ
authors.lastname: Lee-Lin
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Vinton
authors.forename: Gabriel
authors.initials: G
authors.lastname: Renaud
authors.forename: Stacie K
authors.initials: SK
authors.lastname: Loftus
authors.forename: Gene
authors.initials: G
authors.lastname: Elliot
authors.forename: Tyra G
authors.initials: TG
authors.lastname: Wolfsberg
authors.forename: Eric D
authors.initials: ED
authors.lastname: Green
authors.forename: Andrew S
authors.initials: AS
authors.lastname: McCallion
authors.forename: William J
authors.initials: WJ
authors.lastname: Pavan
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001665:Binding Sites; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D018014:Gene Transfer Techniques; D016678:Genome; D006609:High Mobility Group Proteins / Q000235:genetics* / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D009432:Neural Crest / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D055757:SOXE Transcription Factors; D012583:Schwann Cells / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse; D014157:Transcription Factors
references.citation: Nat Genet. 2000 Oct;26(2):225-8
references.pmid: 11017083
references.citation: PLoS Biol. 2007 Sep;5(9):e234
references.pmid: 17803355
references.citation: Genome Res. 2005 Aug;15(8):1061-72
references.pmid: 16024824
references.citation: Development. 2000 Feb;127(3):515-25
references.pmid: 10631172
references.citation: Science. 2006 Apr 14;312(5771):276-9
references.pmid: 16556802
references.citation: FEBS Lett. 1998 Aug 7;432(3):168-72
references.pmid: 9720918
references.citation: Nucleic Acids Res. 2007;35(19):6526-38
references.pmid: 17897962
references.citation: Development. 2001 Oct;128(20):3949-61
references.pmid: 11641219
references.citation: Oncogene. 2003 May 19;22(20):3024-34
references.pmid: 12789277
references.citation: Hum Genet. 1998 Aug;103(2):115-23
references.pmid: 9760192
references.citation: J Biol Chem. 2006 Mar 3;281(9):5453-60
references.pmid: 16373334
references.citation: Development. 2006 Dec;133(23):4619-30
references.pmid: 17065232
references.citation: Mech Dev. 2001 Dec;109(2):253-65
references.pmid: 11731238
references.citation: Genome Res. 2003 Jan;13(1):1-12
references.pmid: 12529301
references.citation: Nat Genet. 1998 Jan;18(1):60-4
references.pmid: 9425902
references.citation: Development. 2001 Nov;128(21):4113-25
references.pmid: 11684650
references.citation: Genes Dev. 2002 Jan 15;16(2):165-70
references.pmid: 11799060
references.citation: Nat Genet. 2004 Apr;36(4):361-9
references.pmid: 15004559
references.citation: Genes Dev. 2001 Jan 1;15(1):66-78
references.pmid: 11156606
references.citation: J Biol Chem. 1998 Sep 4;273(36):23033-8
references.pmid: 9722528
references.citation: Science. 2003 Oct 17;302(5644):413
references.pmid: 14563999
references.citation: Dev Dyn. 1995 Jul;203(3):253-310
references.pmid: 8589427
references.citation: Dev Dyn. 2006 May;235(5):1413-32
references.pmid: 16586440
references.citation: Development. 2003 Dec;130(23):5681-93
references.pmid: 14522876
references.citation: Nat Immunol. 2004 Aug;5(8):768-74
references.pmid: 15282556
references.citation: J Pediatr. 1981 Sep;99(3):432-5
references.pmid: 7264803
references.citation: PLoS One. 2007 Apr 11;2(4):e366
references.pmid: 17426814
references.citation: J Natl Cancer Inst. 2002 Mar 20;94(6):446-54
references.pmid: 11904317
references.citation: Nucleic Acids Res. 2000 Aug 15;28(16):3047-55
references.pmid: 10931919
references.citation: Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5161-5
references.pmid: 9560246
references.citation: J Neurosci. 1998 Jan 1;18(1):237-50
references.pmid: 9412504
references.citation: Nat Protoc. 2006;1(3):1297-305
references.pmid: 17406414
references.citation: Genome Res. 2008 Feb;18(2):252-60
references.pmid: 18071029
references.citation: Ann Neurol. 1999 Sep;46(3):313-8
references.pmid: 10482261
references.citation: Dev Biol. 1986 Aug;116(2):451-66
references.pmid: 3525281
references.citation: Nat Genet. 1998 Feb;18(2):171-3
references.pmid: 9462749
references.citation: J Neurochem. 1994 Nov;63(5):1646-57
references.pmid: 7523597
references.citation: Hum Mol Genet. 2006 Jan 15;15(2):259-71
references.pmid: 16330480
references.citation: Pediatr Dev Pathol. 1999 Nov-Dec;2(6):559-69
references.pmid: 10508880