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Composite co-activator ARC mediates chromatin-directed transcriptional activation

Nature volume 398, pages 828–832 (1999)Cite this article

Abstract

Gene activation in eukaryotes is regulated by complex mechanisms in which the recruitment and assembly of the transcriptional machinery is directed by gene- and cell-type-specific DNA-binding proteins1. When DNA is packaged into chromatin, the regulation of gene activation requires new classes of chromatin-targeting activity2. In humans, a multisubunit cofactor functions in a chromatin-selective manner to potentiate synergistic gene activation by the transcriptional activators SREBP-1a and Sp1 (ref. 3). Here we show that this activator-recruited cofactor (ARC) interacts directly with several different activators, including SREBP-1a, VP16 and the p65 subunit of NF-κB, and strongly enhances transcription directed by these activators in vitro with chromatin-assembled DNA templates. The ARC complex consists of 16 or more subunits; some of these are novel gene products, whereas others are present in other multisubunit cofactors, such as CRSP4, NAT5 and mammalian Mediator6. Detailed analysis indicates that the ARC complex is probably identical to the nuclear hormone-receptor cofactor DRIP7. Thus, ARC/DRIP is a large composite co-activator that belongs to a family of related cofactors and is targeted by different classes of activator to mediate transcriptional stimulation.

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Figure 1: Purification of ARC.
Figure 2: ARC potentiates chromatin-dependent transcriptional activation by several different activators.
Figure 3: Composition of ARC and identity of subunits.
Figure 4: CDK8 and RNA Pol II are not components of ARC.

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Acknowledgements

We thank P. Kaufman, J. Kadonaga, B. Lemon, J. Zwicker, S. Ryu, A. Ladurner and M. Rabenstein for critical reading of the manuscript; R. Burgess for providing the 8WG16 cell line; Z. Cao for the NF-κB p65 subunit; B. Lemon for the purified core Pol II and DRIPs; W. Dynan for the plasmid encoding GST–CTD; S. Triezenberg for plasmids containing VP16 point mutations; R. Kornberg for the antibody against human Med7; S. Ryu for antibodies against CRSP subunits; and A. Ladurner for helping with sequence comparisons. This work was funded by grants from the NIH and HHMI.

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Authors and Affiliations

  1. Howard Hughes Medical Institute Department of Molecular and Cell Biology, University of California, 401 Barker Hall, Berkeley, 94720 , California, USA

    Anders M. Näär, Pierre A. Beaurang, Sharleen Zhou & Robert Tjian

  2. Morse Institute for Molecular Genetics Department of Microbiology and Immunology, State University of New York Health Science Center at Brooklyn, 450 Clarkson Ave, Box 44, Brooklyn, 11203, New York, USA

    Shaji Abraham & William Solomon

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Näär, A., Beaurang, P., Zhou, S. et al. Composite co-activator ARC mediates chromatin-directed transcriptional activation. Nature 398, 828–832 (1999). https://doi.org/10.1038/19789

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