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The BEN domain is a novel sequence-specific DNA-binding domain conserved in neural transcriptional repressors.
- Source :
-
Genes & development [Genes Dev] 2013 Mar 15; Vol. 27 (6), pp. 602-14. Date of Electronic Publication: 2013 Mar 06. - Publication Year :
- 2013
-
Abstract
- We recently reported that Drosophila Insensitive (Insv) promotes sensory organ development and has activity as a nuclear corepressor for the Notch transcription factor Suppressor of Hairless [Su(H)]. Insv lacks domains of known biochemical function but contains a single BEN domain (i.e., a "BEN-solo" protein). Our chromatin immunoprecipitation (ChIP) sequencing (ChIP-seq) analysis confirmed binding of Insensitive to Su(H) target genes in the Enhancer of split gene complex [E(spl)-C]; however, de novo motif analysis revealed a novel site strongly enriched in Insv peaks (TCYAATHRGAA). We validate binding of endogenous Insv to genomic regions bearing such sites, whose associated genes are enriched for neural functions and are functionally repressed by Insv. Unexpectedly, we found that the Insv BEN domain binds specifically to this sequence motif and that Insv directly regulates transcription via this motif. We determined the crystal structure of the BEN-DNA target complex, revealing homodimeric binding of the BEN domain and extensive nucleotide contacts via α helices and a C-terminal loop. Point mutations in key DNA-contacting residues severely impair DNA binding in vitro and capacity for transcriptional regulation in vivo. We further demonstrate DNA-binding and repression activities by the mammalian neural BEN-solo protein BEND5. Altogether, we define novel DNA-binding activity in a conserved family of transcriptional repressors, opening a molecular window on this extensive gene family.
- Subjects :
- Amino Acid Sequence
Animals
Base Sequence
Co-Repressor Proteins chemistry
Co-Repressor Proteins genetics
Co-Repressor Proteins metabolism
DNA-Binding Proteins chemistry
DNA-Binding Proteins genetics
Drosophila Proteins genetics
Gene Expression Regulation, Developmental
Nervous System embryology
Protein Binding
Protein Structure, Quaternary
Protein Structure, Tertiary
Repressor Proteins chemistry
Repressor Proteins genetics
Repressor Proteins metabolism
Sequence Alignment
DNA-Binding Proteins metabolism
Drosophila embryology
Drosophila genetics
Drosophila Proteins chemistry
Drosophila Proteins metabolism
Models, Molecular
Subjects
Details
- Language :
- English
- ISSN :
- 1549-5477
- Volume :
- 27
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Genes & development
- Publication Type :
- Academic Journal
- Accession number :
- 23468431
- Full Text :
- https://doi.org/10.1101/gad.213314.113