A multiprotein complex consisting of the cellular coactivator p300, AP-1/ATF, as well as NF-kappa B is responsible for the activation of the mouse major histocompatibility class I (H-2K(b)) enhancer A

作者：Brockmann D^*; Putzer BM; Lipinski KS; Schmucker U; Esche H

来源：Gene Expression, 1999, 8(1): 1-18.

• AP-1/ATF
• MHC class I
• NF-kappa B
• p300

Major histocompatibility complex (MHC) class I genes encode highly polymorphic antigens that play an essential role in a number of immunological processes. Their expression is activated in response to a variety of signals and is mediated through several promoter elements among which the enhancer A is one of the key control regions. It contains binding sites for several transcription factors, for example: (i) a well-characterized binding site for rel/NF-kappa B transcription factors in its 3'-end (the H2TF1 or kappa B-1 element), (ii) a second KB site (the kappa B-2 element), which is located immediately adjacent 5' to the H2TF1 element and which is recognized by p65/relA in the human HLA system, and (iii) an AP-1/ATF recognition sequence in the 5' end (EnA-TRE), Here we demonstrate that latter element is bound by at least two distinct heterodimers of the AP-1/ATF transcription factor family, namely c-Jun/ATF-2 and c-Jun/Fra2. Moreover, our data reveal that the enhancer A is simultaneously bound by AP-1/ATF and rel/NF-kappa B transcription factors and that the cellular coactivator p300, which enhances enhancer A-driven reporter gene expression if cotransfected, is recruited to the enhancer A through this multiprotein complex. In contrast to the complete enhancer A, neither the EnA-TRE nor the H2TF1 element on their own are able to confer activation on a heterologous promoter in response to the phorbol ester tumor promoter TPA or the cytokine TNF alpha. Moreover, deletion of any one of the enhancer A control elements results in a dramatic loss of its inducibility by TNF alpha, and point mutations in either the EnA-TRE or the H2TF1 element lead to the loss of AP-1/ATF or NF-kappa B binding, respectively, and to the loss of enhancer A inducibility. Therefore, we conclude that the enhancer A is synergistically activated through a multiprotein complex containing AP-1/ATF, NF-kappa B transcription factors as well as the cellular coactivator p300.

• 出版日期1999