title: neptune, a Krüppel-like transcription factor that participates in primitive erythropoiesis in Xenopus.
abstract: The specification of the erythroid lineage from hematopoietic stem cells requires the expression and activity of lineage-specific transcription factors. One transcription factor family that has several members involved in hematopoiesis is the Krüppel-like factor (KLF) family [1]. For example, erythroid KLF (EKLF) regulates beta-globin expression during erythroid differentiation [2-6]. KLFs share a highly conserved zinc finger-based DNA binding domain (DBD) that mediates binding to CACCC-box and GC-rich sites, both of which are frequently found in the promoters of hematopoietic genes. Here, we identified a novel Xenopus KLF gene, neptune, which is highly expressed in the ventral blood island (VBI), cranial ganglia, and hatching and cement glands. neptune expression is induced in response to components of the BMP-4 signaling pathway in injected animal cap explants. Similar to its family member, EKLF, Neptune can bind CACCC-box and GC-rich DNA elements. We show that Neptune cooperates with the hematopoietic transcription factor XGATA-1 to enhance globin induction in animal cap explants. A fusion protein comprised of Neptune's DBD and the Drosophila engrailed repressor domain suppresses the induction of globin in ventral marginal zones and in animal caps. These studies demonstrate that Neptune is a positive regulator of primitive erythropoiesis in Xenopus.
authors.affiliation: Division of Hematology/Oncology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Huber
authors.forename: A C
authors.initials: AC
authors.lastname: Perkins
authors.forename: A E
authors.initials: AE
authors.lastname: Deconinck
authors.forename: F Y
authors.initials: FY
authors.lastname: Chan
authors.forename: P E
authors.initials: PE
authors.lastname: Mead
authors.forename: L I
authors.initials: LI
authors.lastname: Zon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D004920:Erythropoiesis / Q000502:physiology*; D015870:Gene Expression; D006410:Hematopoiesis; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D008969:Molecular Sequence Data; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; C443840:KLF17 protein, Xenopus; D051741:Kruppel-Like Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus