Deciphering the DNA code for the function of the Drosophila polydactyl zinc finger protein Suppressor of Hairy-wing.
Polydactyl zinc finger (ZF) proteins have prominent roles in gene regulation and often execute multiple regulatory functions. To understand how these proteins perform varied regulation, we studiedDrosophila Suppressor of Hairy-wing [Su(Hw)], an exemplar multifunctional polydactyl ZF protein. We identified separation-of-function (SOF) alleles that encode proteins disrupted in a single ZF that retain one of the Su(Hw) regulatory activities. Through extended in vitro analyses of the Su(Hw) ZF domain, we show that clusters of ZFs bind individual modules within a compound DNA consensus sequence. Through in vivo analysis of SOF mutants, we find that Su(Hw) genomic sites separate into sequence subclasses comprised of combinations of modules, with subclasses enriched for different chromatin features. These data suggest a Su(Hw) code, wherein DNA binding dictates its cofactor recruitment and regulatory output. We propose that similar DNA codes might be used to confer multiple regulatory functions of other polydactyl ZF proteins.
Interdisciplinary Graduate Program in Molecular and Cellular Biology, University of Iowa, Iowa City, IA 52242, USA.
Ryan M
RM
Baxley
Department of Biochemistry, University of Iowa, Iowa City, IA 52242, USA.
James D
JD
Bullard
Department of Biochemistry, University of Iowa, Iowa City, IA 52242, USA.
Michael W
MW
Klein
Department of Biochemistry, University of Iowa, Iowa City, IA 52242, USA.
Ashley G
AG
Fell
Department of Biochemistry, University of Iowa, Iowa City, IA 52242, USA.
Joel A
JA
Morales-Rosado
Department of Biochemistry, University of Iowa, Iowa City, IA 52242, USA.
Tingting
T
Duan
Interdisciplinary Graduate Program in Molecular and Cellular Biology, University of Iowa, Iowa City, IA 52242, USA.|Department of Biochemistry, University of Iowa, Iowa City, IA 52242, USA.
Pamela K
PK
Geyer
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002843:Chromatin / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D005020:Ethyl Methanesulfonate / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D008297:Male; D009153:Mutagens / Q000494:pharmacology; D009154:Mutation; D010641:Phenotype; D011485:Protein Binding; D000072417:Protein Domains; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D016335:Zinc Fingers
D002843:Chromatin; D029721:Drosophila Proteins; D009153:Mutagens; D012097:Repressor Proteins; C083738:su(Hw) protein, Drosophila; D004247:DNA; D005020:Ethyl Methanesulfonate