Drosophila transcription factor Tramtrack69 binds MEP1 to recruit the chromatin remodeler NuRD.
ATP-dependent chromatin-remodeling complexes (remodelers) are essential regulators of chromatin structure and gene transcription. How remodelers can act in a gene-selective manner has remained enigmatic. A yeast two-hybrid screen for proteins binding the Drosophila transcription factor Tramtrack69 (TTK69) identified MEP1. Proteomic characterization revealed that MEP1 is a tightly associated subunit of the NuRD remodeler, harboring the Mi2 enzymatic core ATPase. In addition, we identified the fly homolog of human Deleted in oral cancer 1 (DOC1), also known as CDK2-associated protein 1 (CDK2AP1), as a bona fide NuRD subunit. Biochemical and genetic assays supported the functional association between MEP1, Mi2, and TTK69. Genomewide expression analysis established that TTK69, MEP1, and Mi2 cooperate closely to control transcription. The TTK69 transcriptome profile correlates poorly with remodelers other than NuRD, emphasizing the selectivity of remodeler action. On the genes examined, TTK69 is able to bind chromatin in the absence of NuRD, but targeting of NuRD is dependent on TTK69. Thus, there appears to be a hierarchical relationship in which transcription factor binding precedes remodeler recruitment.
Reddy
B Ashok
BA
Department of Biochemistry, Center for Biomedical Genetics, Erasmus University Medical Center, Rotterdam, Netherlands.
Bajpe
Prashanth Kumar
PK
Bassett
Andrew
A
Moshkin
Yuri M
YM
Kozhevnikova
Elena
E
Bezstarosti
Karel
K
Demmers
Jeroen A A
JA
Travers
Andrew A
AA
Verrijzer
C Peter
CP
D000818:Animals; D001483:Base Sequence; D042002:Chromatin Assembly and Disassembly; D017931:DNA Primers / Q000235:genetics; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D017344:Genes, Insect; D006801:Humans; D066298:In Vitro Techniques; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D021122:Protein Subunits; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D017931:DNA Primers; D029721:Drosophila Proteins; D021122:Protein Subunits; D012097:Repressor Proteins; C075878:ttk protein, Drosophila; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex