Abstract
An array of regulatory protein and multi-subunit cofactors has been identified1 that directs eukaryotic gene transcription. However, establishing the specific functions of various related cofactors has been difficult owing to the limitations inherent in assaying transcription in animals and cells indirectly. Here we describe, using an integrated chromatin-dependent reconstituted transcription reaction, the purification and identification of a multi-subunit cofactor (PBAF)2 that is necessary for ligand-dependent transactivation by nuclear hormone receptors. A highly related cofactor, human SWI/SNF3, and the ISWI-containing chromatin-remodelling complex ACF4 both fail to potentiate transcription. We also show that transcriptional activation mediated by nuclear hormone receptors requires TATA-binding protein (TBP)-associated factors (TAFs) as well as the multi-subunit cofactors ARC5/CRSP6. These studies demonstrate functional selectivity amongst highly related complexes involved in gene regulation and help define a more complete set of factors and cofactors required to activate transcription.
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Acknowledgements
We thank R. Bell and M. Haggart for technical assistance; W. Wang for providing affinity-purified antibodies raised against BAF180; G. Crabtree for antibodies raised against BRG1 and multiple BAFs; N. Tanese for antibodies raised against BAF250; R. Kingston and A. Imbalzano for antibodies raised against BRM; D. Fyodorov and J. Kadonaga for providing recombinant viruses for expression of ACF and for purified rACF used in initial experiments; S. Ryu for purified TFIIH, rPC4, rTopo I, and rTBP, as well as the G3B-CAT plasmid; A. Näär for purified rSREBP-1a as well as LDLR-CAT and GST-activation domain expression plasmids; J.-L. Chen for the PPARγ cDNA and ligand; L. Freedman, R. Freiman, J. Kadonaga, P. Kaufman, M. Marr, D. Taatjes, and W. Wang for comments on the manuscript, and all members of our laboratory for helpful discussions and technical advice. B.L. was recipient of a National Research Service Award during most of this work.
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Lemon, B., Inouye, C., King, D. et al. Selectivity of chromatin-remodelling cofactors for ligand-activated transcription. Nature 414, 924–928 (2001). https://doi.org/10.1038/414924a
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DOI: https://doi.org/10.1038/414924a
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