title: Krüppel-like factor 2 regulated gene expression in mouse embryonic yolk sac erythroid cells.
abstract: KLF2 is a Krüppel-like zinc-finger transcription factor required for blood vessel, lung, T-cell and erythroid development. KLF2-/- mice die by embryonic day 14.5 (E14.5), due to hemorrhaging and heart failure. In KLF2-/- embryos, β-like globin gene expression is reduced, and E10.5 erythroid cells exhibit abnormal morphology. In this study, other genes regulated by KLF2 were identified by comparing E9.5 KLF2-/- and wild-type (WT) yolk sac erythroid precursor cells, using laser capture microdissection and microarray assays. One hundred and ninety-six genes exhibited significant differences in expression between KLF2-/- and WT; eighty-nine of these are downregulated in KLF2-/-. Genes involved in cell migration, differentiation and development are over-represented in the KLF2-regulated gene list. The SOX2 gene, encoding a pluripotency factor, is regulated by KLF2 in both ES and embryonic erythroid cells. Previous work had identified genes with erythroid-enriched expression in the yolk sac. The erythroid-enriched genes reelin, adenylate cyclase 7, cytotoxic T lymphocyte-associated protein 2 alpha, and CD24a antigen are downregulated in KLF2-/- compared to WT and are therefore candidates for controlling primitive erythropoiesis. Each of these genes contains a putative KLF2 binding site(s) in its promoter and/or an intron. Reelin has an established role in neuronal development. Luciferase reporter assays demonstrated that KLF2 directly transactivates the reelin promoter in erythroid cells, validating this approach to identify KLF2 target genes.
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Latasha C
authors.initials: LC
authors.lastname: Redmond
authors.forename: Catherine I
authors.initials: CI
authors.lastname: Dumur
authors.forename: Kellie J
authors.initials: KJ
authors.lastname: Archer
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Grayson
authors.forename: Jack L
authors.initials: JL
authors.lastname: Haar
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Lloyd
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D002460:Cell Line; D041905:Erythroid Cells / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D020014:K562 Cells; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics; D015017:Yolk Sac / Q000166:cytology / Q000196:embryology*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases