TAILIEUCHUNG - Báo cáo khoa học: Slc12a2 is a direct target of two closely related homeobox proteins, Six1 and Six4

Sixgenes are homologs ofDrosophila sine oculisand encode transcription factors that are characterized by a conserved Six domain and homeo-domain. Of the six family members (Six1–Six6) in mice, Six1and Six4 show similar expression patterns during embryogenesis. Six1 –⁄ – mice show defective formation of various organs such as inner ear, nose, skeletal mus-cle, kidney and thymus, whereasSix4 –⁄ – mice show little anomaly in organo-genesis. | iFEBS Journal Slc12a2 is a direct target of two closely related homeobox proteins Six1 and Six4 Zen-ichi Ando Shigeru Sato Keiko Ikeda and Kiyoshi Kawakami Division of Biology Center for Molecular Medicine Jichi MedicalSchool Tochigi Japan Keywords dorsal root ganglia Six1 Six4 Slc12a2 transcriptional targets Correspondence K. Kawakami Division of Biology Center for Molecular Medicine Jichi Medical School Yakushiji Minamikawachi Tochigi 329-0498 Japan Fax 81 285 44 5476 Tel 81 285 58 7312 E-mail kkawakam@ Received 13 December 2004 revised 15 March 2005 accepted 11 April 2005 doi Six genes are homologs of Drosophila sine oculis and encode transcription factors that are characterized by a conserved Six domain and homeo-domain. Of the six family members Six1-Six6 in mice Sixl and Six4 show similar expression patterns during embryogenesis. Sixl mice show defective formation of various organs such as inner ear nose skeletal muscle kidney and thymus whereas Six4 mice show little anomaly in organogenesis. To understand the molecular basis for the differential function of Sixl and Six4 in vivo we screened target genes of Six1 and Six4 and found that Six1 and Six4 differentially regulated a set of target genes. Gel-retardation assays indicated that the promoter region of one of the targets sodiumpotassium-chloride cotransporter 1 Slc12a2 contains multiple Six1-binding sites and one common binding site of Six1 and Six4 suggesting that the DNA-binding specificity of Six1 is distinct from that of Six4. This underlies the differential regulation of common target genes by Six1 and Six4. Furthermore in situ hybridization demonstrated that the expression of Slc12a2 was reduced in the developing dorsal root ganglia of Six1 Six4 mice suggesting that Six1 and Six4 regulate Slc12a2 in vivo. The Six homeobox gene is characterized by the conserved Six domain SD and homeodomain HD both of which are required for specific DNA binding 1 2 . The .

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