title: Mouse homolog of SALL1, a causative gene for Townes-Brocks syndrome, binds to A/T-rich sequences in pericentric heterochromatin via its C-terminal zinc finger domains.
abstract: The Spalt (sal) gene family is conserved from Drosophila to humans. Mutations of human SALL1 cause Townes-Brocks syndrome, with features of ear, limb, anal, renal and heart anomalies. Sall1, a murine homolog of SALL1, is essential for kidney formation, and both Sall1 and SALL1 localize to heterochromatin in the nucleus. Here, we present a molecular mechanism for the heterochromatin localization of Sall1. Mutation analyses revealed that the 7th-10th C-terminal double zinc finger motifs were required for the localization. A recombinant protein of the most C-terminal double zinc finger (9th-10th) bound to specific A/T-rich sequences. Furthermore, Sall1 associated with A/T-rich sequences of the major satellite DNA in heterochromatin. Thus Sall1 may bind to A/T-rich sequences of the major satellite DNA via its C-terminal double zinc fingers, thereby mediating its localization to heterochromatin.
authors.affiliation: Division of Integrative Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Yamashita
authors.forename: Akira
authors.initials: A
authors.lastname: Sato
authors.forename: Makoto
authors.initials: M
authors.lastname: Asashima
authors.forename: Pi-Chao
authors.initials: PC
authors.lastname: Wang
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Nishinakamura
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D004276:DNA, Satellite; D024202:Electrophoretic Mobility Shift Assay; D006570:Heterochromatin / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D013577:Syndrome; D014157:Transcription Factors / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D004276:DNA, Satellite; D006570:Heterochromatin; C491254:Sall1 protein, mouse; D014157:Transcription Factors