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Modulation of heat shock gene expression by the TAC1 chromatin-modifying complex

Nature Cell Biology volume 6, pages 162–167 (2004)Cite this article

Abstract

Rapid induction of the Drosophila melanogaster heat shock gene hsp70 is achieved through the binding of heat shock factor1 (HSF) to heat shock elements (HSEs) located upstream of the transcription start site2 (reviewed in ref. 3). The subsequent recruitment of several other factors4,5,6,7,8, including Spt5, Spt6 and FACT, is believed to facilitate Pol II elongation through nucleosomes downstream of the start site9,10,11. Here, we report a novel mechanism of heat shock gene regulation that involves modifications of nucleosomes by the TAC1 histone modification complex12. After heat stress, TAC1 is recruited to several heat shock gene loci, where its components are required for high levels of gene expression. Recruitment of TAC1 to the 5′-coding region of hsp70 seems to involve the elongating Pol II complex. TAC1 has both histone H3 Lys 4-specific (H3-K4) methyltransferase (HMTase) activity and histone acetyltransferase activity through Trithorax (Trx) and CREB-binding protein (CBP), respectively. Consistently, TAC1 is required for methylation and acetylation of nucleosomal histones in the 5′-coding region of hsp70 after induction, suggesting an unexpected role for TAC1 during transcriptional elongation.

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Figure 1: Recruitment of TAC1 components to heat shock gene loci on salivary gland polytene chromosomes.
Figure 2: TAC1 is associated with the coding region of the actively transcribed hsp70 gene.
Figure 3: Heat shock RNA induction is decreased in trx and dCBP (nej) mutant embryos.
Figure 4: TAC1-dependent modifications of histones in the hsp70 gene after heat exposure.
Figure 5: TAC1-dependent modifications of histones in hsp70 in trxZ11 mutant embryos.

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Acknowledgements

We would like to thank J. Lis, A. Shearn, C. Wu, F. Winston, S. Lindquist, C. Wu, T.-S. Hsieh, D. Gilmour and T. Breen for antibodies and mutant stocks, and J.B. Jaynes for critical remarks on the manuscript. S.P. was supported by a training program from the National Cancer Institute (NCI) (CA009678). This work was supported by a grant (CA50507) from the NCI to A.M.

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Author notes

  1. Sergei Tillib

    Present address: Institute of Gene Biology, Russian Academy of Sciences, Moscow, 117334, Russia

  2. Svetlana Petruk, Yurii Sedkov and Alexander Mazo: These authors contributed equally to this work.

Authors and Affiliations

  1. Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, 19107, PA, USA

    Sheryl T. Smith, Svetlana Petruk, Yurii Sedkov, Elizabeth Cho, Sergei Tillib & Alexander Mazo

  2. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel

    Eli Canaani

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Correspondence to Alexander Mazo.

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Smith, S., Petruk, S., Sedkov, Y. et al. Modulation of heat shock gene expression by the TAC1 chromatin-modifying complex. Nat Cell Biol 6, 162–167 (2004). https://doi.org/10.1038/ncb1088

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