A dimer-specific function of the transcription factor NFATp.
The transcription factor NFATp integrates multiple signal transduction pathways through coordinate binding with basic-region leucine zipper (bZIP) proteins and other transcription factors. The NFATp monomer, even in the absence of its activation domains, recruits bZIP proteins to canonical NFAT-bZIP composite DNA elements. By contrast, the NFATp dimer and its bZIP partner bind noncooperatively to the NFAT-bZIP element of the tumor necrosis factor (TNF) gene promoter. This observation raises the possibility that the function of the activation domains of NFATp is dimer-specific. Here, we determine the consensus DNA binding site of the NFATp dimer, describe monomer- and dimer-specific NFATp-DNA contact patterns, and demonstrate that NFATp dimerization and dimer-specific activation subdomains are required for transcriptional activation from the TNF NFAT-bZIP element. We also show that these NFATp subdomains interact with the coactivator CBP (CREB-binding protein), which is required for NFATp-dependent TNF gene transcription. Thus, the context-specific function of the activation domains of NFAT can be potentiated by DNA-directed dimerization.
Falvo
James V
JV
Immune Disease Institute and Harvard Medical School, 800 Huntington Avenue, Boston, MA 02115, USA.
Lin
Charles H
CH
Tsytsykova
Alla V
AV
Hwang
Peter K
PK
Thanos
Dimitris
D
Goldfeld
Anne E
AE
Maniatis
Tom
T
D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism; D050882:CREB-Binding Protein / Q000378:metabolism; D016384:Consensus Sequence; D004247:DNA / Q000378:metabolism; D019281:Dimerization; D024202:Electrophoretic Mobility Shift Assay; D050778:NFATC Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D050976:Basic-Leucine Zipper Transcription Factors; D050778:NFATC Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D050882:CREB-Binding Protein