An ancient protein-DNA interaction underlying metazoan sex determination [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 572.8 Biochemical genetics
• Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2015
• Mô tả vật lý: Size: p. 442-451 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 261152
• Chủ đề: 1. 59 basic biological sciences; 2. 60 applied life sciences; 3. Dm domain; 4. Dmrt protein; 5. Dmrt1; 6. Dna-binding proteins; 7. Sex determination; 8. Transcription factors

Tóm tắt

DMRT transcription factors are deeply conserved regulators of metazoan sexual development. They share the DM DNA-binding domain, a unique intertwined double zinc-binding module followed by a C-terminal recognition helix, which binds a pseudopalindromic target DNA. In this paper, we show that DMRT proteins use a unique binding interaction, inserting two adjacent antiparallel recognition helices into a widened DNA major groove to make base-specific contacts. Versatility in how specific base contacts are made allows human DMRT1 to use multiple DNA binding modes (tetramer, trimer and dimer). Chromatin immunoprecipitation with exonuclease treatment (ChIP-exo) indicates that multiple DNA binding modes also are used in vivo. We show that mutations affecting residues crucial for DNA recognition are associated with an intersex phenotype in flies and with male-to-female sex reversal in humans. Finally, our results illuminate an ancient molecular interaction underlying much of metazoan sexual development.