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The homeodomain transcription factor NK-4 acts as either a transcriptional activator or repressor and interacts with the p300 coactivator and the Groucho corepressor.

Authors
Choi, CY | Lee, YM  | Kim, YH | Park, T | Jeon, BH | Schulz, RA | Kim, Y
Citation
The Journal of biological chemistry, 274(44). : 31543-31552, 1999
Journal Title
The Journal of biological chemistry
ISSN
0021-92581083-351X
Abstract
NK-4 (tinman) encodes an NK-2 class homeodomain transcription factor that is required for development of the Drosophila dorsal mesoderm, including heart. Genetic evidence suggests its important role in mesoderm subdivision, yet the properties of NK-4 as a transcriptional regulator and the mechanism of gene transcription by NK-4 are not completely understood. Here, we describe its properties as a transcription factor and its interaction with the p300 coactivator and the Groucho corepressor. We demonstrate that NK-4 can activate or repress target genes in cultured cells, depending on functional domains that are conserved between Drosophila melanogaster and Drosophila virilis NK-4 genes. Using GAL4-NK-4 fusion constructs, we have mapped a transcriptional activation domain (amino acids 1-110) and repression domains (amino acids 111-188 and the homeodomain) and found an inhibitory function for the homeodomain in transactivation by NK-4. Furthermore, we demonstrate that NK-4-dependent transactivation is augmented by the p300 coactivator and show that NK-4 physically interacts with p300 via the activation domain. In addition, cotransfection experiments indicate that the repressor activity of NK-4 is strongly enhanced by the Groucho corepressor. Using immunoprecipitation and in vitro pull-down assays, we show that NK-4 directly interacts with the Groucho corepressor, for which the homeodomain is required. Together, our results indicate that NK-4 can act as either a transcriptional activator or repressor and provide the first evidence of NK-4 interactions with the p300 coactivator and the Groucho corepressor.
MeSH

PMID
10531357
Appears in Collections:
Journal Papers > Research Organization > Institute for Medical Sciences
Ajou Authors
이, 영미
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