DOI: 10.1126/science.293.5532.1133. Coordination of a Transcriptional Switch by HMGI(Y) Acetylation

Coordination of a Transcriptional Switch by HMGI(Y) Acetylation

10.1126/science.293.5532.1133

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

Dynamic control of interferon-β (IFN-β) gene expression requires the regulated assembly and disassembly of the enhanceosome, a higher-order nucleoprotein complex formed in response to virus infection. The enhanceosome activates transcription by recruiting the histone acetyltransferase proteins CREB binding protein (CBP) and p 300/ C BP- a ssociated f actors (PCAF)/GCN5, which, in addition to modifying histones, acetylate HMGI(Y), the architectural component required for enhanceosome assembly. We show that the accurate execution of the IFN-β transcriptional switch depends on the ordered acetylation of the high-mobility group I protein HMGI(Y) by PCAF/GCN5 and CBP, which acetylate HMGI(Y) at distinct lysine residues on endogenous promoters. Whereas acetylation of HMGI(Y) by CBP at lysine-65 destabilizes the enhanceosome, acetylation of HMGI(Y) by PCAF/GCN5 at lysine-71 potentiates transcription by stabilizing the enhanceosome and preventing acetylation by CBP.

Bibliography

Munshi, N., Agalioti, T., Lomvardas, S., Merika, M., Chen, G., & Thanos, D. (2001). Coordination of a Transcriptional Switch by HMGI(Y) Acetylation. Science, 293(5532), 1133â1136.

Authors 6

Nikhil Munshi (first)
Theodora Agalioti (additional)
Stavros Lomvardas (additional)
Menie Merika (additional)
Guoying Chen (additional)
Dimitris Thanos (additional)

References 17 Referenced 163

10.1101/sqb.1999.64.149
10.1016/0092-8674(95)90136-1
10.1093/emboj/18.11.3074
10.1016/S0092-8674(00)00169-0
Kim T. K., Kim T. H., Maniatis T., Proc. Natl. Acad. Sci. U.S.A. 95, 12191 (1998). (10.1073/pnas.95.21.12191) / Proc. Natl. Acad. Sci. U.S.A. by Kim T. K. (1998)
10.1016/S1097-2765(00)80028-3
10.1073/pnas.96.23.13108
10.1016/S1097-2765(00)80145-8
Parekh B. S., Maniatis T., Mol. Cell 3, 125 (1998). (10.1016/S1097-2765(00)80181-1) / Mol. Cell by Parekh B. S. (1998)
Relevant data and experimental procedures can be found at Science Online at www.sciencemag.org/cgi/content/full/293/5532/1133/DC1.
HMGI(Y) derivatives were acetylated in vitro as previously described (8) with the following modifications. Substrates were incubated with enzyme and 3 H-labeled acetyl CoA (Sigma St. Louis MO) for 1 hour and fresh enzyme was added every hour for 4 hours. Using 3 H-labeled HMGI(Y) proteins GST pull-down assays were performed essentially as described (3). For peptide competition assays the indicated amount of peptide (obtained from Research Genetics Huntsville AL) was added during incubation of GST-p50 with in vitro translated 35 S-labeled HMGI(Y) (TnT in vitro translation kit; Promega Madison WI).
DNase I footprinting experiments were carried out as described (2). For reactions containing preacetylated HMGI(Y) acetylation was carried out as described above (11) except that cold acetyl-CoA (Pharmacia Peapack NJ) was used in these reactions. HMGI(Y) was acetylated in situ (Fig. 3) according to methods in (8).
Chromatin IP experiments were carried out as described (4).
Sato M., et al., Immunity 13, 539 (2000). (10.1016/S1074-7613(00)00053-4) / Immunity by Sato M. (2000)
Acetylated peptides were synthesized for K65 (Genosys The Woodlands TX) and K71 (Research Genetics) in order to immunize rabbits. Whole rabbit serum was purified by passing it over a column conjugated to the acetylated peptide and then passing the eluant over a column conjugated to the unacetylated peptide in order to deplete nonspecific antibodies. The flow-through was collected and used in Western blots and chromatin IP experiments (Fig. 2 B and C).
Single-letter abbreviations for the amino acid residues are as follows: A Ala; C Cys; D Asp; E Glu; F Phe; G Gly; H His; I Ile; K Lys; L Leu; M Met; N Asn; P Pro; Q Gln; R Arg; S Ser; T Thr; V Val; W Trp; and Y Tyr.
We thank R. Mann and members of the laboratory for critical reading of the manuscript. This work was supported by grants from NIH (1RO1GM54605) the Pew Scholars Program in Biomedical Sciences the March of Dimes and the Irma T. Hirschl Foundation (to D.T.). N.M. was partially supported by the Columbia Medical Scientist Training Program (NIH grant 5-T32-GM07367).

Dates

Type	When
Created	23 years ago (July 27, 2002, 5:39 a.m.)
Deposited	1 year, 7 months ago (Jan. 13, 2024, 3:45 a.m.)
Indexed	2 weeks, 6 days ago (Aug. 5, 2025, 8:26 a.m.)
Issued	24 years ago (Aug. 10, 2001)
Published	24 years ago (Aug. 10, 2001)
Published Print	24 years ago (Aug. 10, 2001)

Funders 0

None

BibTeX

@article{Munshi_2001, title={Coordination of a Transcriptional Switch by HMGI(Y) Acetylation}, volume={293}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.293.5532.1133}, DOI={10.1126/science.293.5532.1133}, number={5532}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Munshi, Nikhil and Agalioti, Theodora and Lomvardas, Stavros and Merika, Menie and Chen, Guoying and Thanos, Dimitris}, year={2001}, month=aug, pages={1133–1136} }

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  "abstract": "<jats:p>\n            Dynamic control of interferon-\u03b2 (IFN-\u03b2) gene expression requires the regulated assembly and disassembly of the enhanceosome, a higher-order nucleoprotein complex formed in response to virus infection. The enhanceosome activates transcription by recruiting the histone acetyltransferase proteins CREB binding protein (CBP) and\n            <jats:underline>p</jats:underline>\n            300/\n            <jats:underline>C</jats:underline>\n            BP-\n            <jats:underline>a</jats:underline>\n            ssociated\n            <jats:underline>f</jats:underline>\n            actors (PCAF)/GCN5, which, in addition to modifying histones, acetylate HMGI(Y), the architectural component required for enhanceosome assembly. We show that the accurate execution of the IFN-\u03b2 transcriptional switch depends on the ordered acetylation of the high-mobility group I protein HMGI(Y) by PCAF/GCN5 and CBP, which acetylate HMGI(Y) at distinct lysine residues on endogenous promoters. Whereas acetylation of HMGI(Y) by CBP at lysine-65 destabilizes the enhanceosome, acetylation of HMGI(Y) by PCAF/GCN5 at lysine-71 potentiates transcription by stabilizing the enhanceosome and preventing acetylation by CBP.\n          </jats:p>",
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