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A multiprotein complex consisting of the cellular coactivator p300, AP-1/ATF, as well as NF-kappaB is responsible for the activation of the mouse major histocompatibility class I (H-2K(b)) enhancer A.
Gene Expr. 1999; 8(1):1-18.GE

Abstract

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-kappaB transcription factors in its 3'-end (the H2TF1 or kappaB1 element), (ii) a second kappaB site (the kappaB2 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-kappaB 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 TNFalpha. Moreover, deletion of any one of the enhancer A control elements results in a dramatic loss of its inducibility by TNFalpha, and point mutations in either the EnA-TRE or the H2TF1 element lead to the loss of AP-1/ATF or NF-kappaB 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-kappaB transcription factors as well as the cellular coactivator p300.

Authors+Show Affiliations

Institute of Molecular Biology (Cancer Research), University of Essen Medical School, Germany. dieter.brockmann@uni-essen.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10543727

Citation

Brockmann, D, et al. "A Multiprotein Complex Consisting of the Cellular Coactivator P300, AP-1/ATF, as Well as NF-kappaB Is Responsible for the Activation of the Mouse Major Histocompatibility Class I (H-2K(b)) Enhancer A." Gene Expression, vol. 8, no. 1, 1999, pp. 1-18.
Brockmann D, Pützer BM, Lipinski KS, et al. A multiprotein complex consisting of the cellular coactivator p300, AP-1/ATF, as well as NF-kappaB is responsible for the activation of the mouse major histocompatibility class I (H-2K(b)) enhancer A. Gene Expr. 1999;8(1):1-18.
Brockmann, D., Pützer, B. M., Lipinski, K. S., Schmücker, U., & Esche, H. (1999). A multiprotein complex consisting of the cellular coactivator p300, AP-1/ATF, as well as NF-kappaB is responsible for the activation of the mouse major histocompatibility class I (H-2K(b)) enhancer A. Gene Expression, 8(1), 1-18.
Brockmann D, et al. A Multiprotein Complex Consisting of the Cellular Coactivator P300, AP-1/ATF, as Well as NF-kappaB Is Responsible for the Activation of the Mouse Major Histocompatibility Class I (H-2K(b)) Enhancer A. Gene Expr. 1999;8(1):1-18. PubMed PMID: 10543727.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A multiprotein complex consisting of the cellular coactivator p300, AP-1/ATF, as well as NF-kappaB is responsible for the activation of the mouse major histocompatibility class I (H-2K(b)) enhancer A. AU - Brockmann,D, AU - Pützer,B M, AU - Lipinski,K S, AU - Schmücker,U, AU - Esche,H, PY - 1999/10/30/pubmed PY - 1999/10/30/medline PY - 1999/10/30/entrez SP - 1 EP - 18 JF - Gene expression JO - Gene Expr VL - 8 IS - 1 N2 - 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-kappaB transcription factors in its 3'-end (the H2TF1 or kappaB1 element), (ii) a second kappaB site (the kappaB2 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-kappaB 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 TNFalpha. Moreover, deletion of any one of the enhancer A control elements results in a dramatic loss of its inducibility by TNFalpha, and point mutations in either the EnA-TRE or the H2TF1 element lead to the loss of AP-1/ATF or NF-kappaB 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-kappaB transcription factors as well as the cellular coactivator p300. SN - 1052-2166 UR - https://www.unboundmedicine.com/medline/citation/10543727/A_multiprotein_complex_consisting_of_the_cellular_coactivator_p300_AP_1/ATF_as_well_as_NF_kappaB_is_responsible_for_the_activation_of_the_mouse_major_histocompatibility_class_I__H_2K_b___enhancer_A_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/10543727/ DB - PRIME DP - Unbound Medicine ER -