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Flinn, Elisabeth M
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Publications (2 of 2) Show all publications
Flinn, E. M., Wallberg, A. E., Hermann, S., Grant, P. A., Workman, J. L. & Wright, A. P. (2002). Recruitment of Gen5-containing complexes during c-Myc-dependent gene activation - Structure and function aspects. Journal of Biological Chemistry, 277(26), 23399-23406
Open this publication in new window or tab >>Recruitment of Gen5-containing complexes during c-Myc-dependent gene activation - Structure and function aspects
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2002 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 277, no 26, p. 23399-23406Article in journal (Refereed) Published
Abstract [en]

The N-terminal domain of c-Myc plays a key role in cellular transformation and is involved in both activation and repression of target genes as well as in modulated proteolysis of c-Myc via the proteasome. Given this functional complexity, it has been difficult to clarify the structures within the N terminus that contribute to these different processes as well as the mechanisms by which they function. We have used a simplified yeast model system to identify the primary determinants within the N terminus for W chromatin remodeling of a promoter, (ii) gene activation from a chromatin template in vivo, and (iii) interaction with highly purified Gcn5 complexes as well as other chromatin-remodeling complexes in vitro. The results identify two regions that contain autonomous chromatin opening and gene activation activity, but both regions are required for efficient interaction with chromatin-remodeling complexes in vitro. The conserved Myc boxes do not play a direct role in gene activation, and Myc box II is not generally required for in vitro interactions with remodeling complexes. The yeast SAGA complex, which is orthologous to the human GCN5-TRRAP complex that interacts with Myc in human cells, plays a role in Myc-mediated chromatin opening at the promoter but may also be involved in later steps of gene activation.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:sh:diva-15799 (URN)10.1074/jbc.M201704200 (DOI)000176475700040 ()11973336 (PubMedID)2-s2.0-0037189508 (Scopus ID)
Available from: 2012-03-08 Created: 2012-03-07 Last updated: 2017-12-07Bibliographically approved
Bergh, F. T., Flinn, E. M., Svaren, J., Wright, A. P. & Horz, W. (2000). Comparison of nucleosome remodeling by the yeast transcription factor Pho4 and the glucocorticoid receptor. Journal of Biological Chemistry, 275(12), 9035-9042
Open this publication in new window or tab >>Comparison of nucleosome remodeling by the yeast transcription factor Pho4 and the glucocorticoid receptor
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2000 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 275, no 12, p. 9035-9042Article in journal (Refereed) Published
Abstract [en]

Chromatin reorganization of the PHO5 and murine mammary tumor virus (MMTV) promoters is triggered by binding of either Pho4 or the glucocorticoid receptor (GR), respectively. In order to compare the ability of Pho4 and GR to remodel chromatin and activate transcription, hybrid promoter constructs were created by insertion of the MMTV B nucleosome sequence into the PHO5 promoter and then transformed into a yeast strain expressing GR, Activation of either Pho4 (by phosphate depletion) or GR (by hormone addition) resulted in only slight induction of hybrid promoter activity. However, simultaneous activation of both Pho4 and GR resulted in synergistic activation to levels exceeding that of the wild type PHO5 promoter. Under these conditions, Pho4 completely disrupted the nucleosome containing its binding site. In contrast, GR had little effect on the stability of the MMTV B nucleosome. A minimal transactivation domain of the GR fused to the Pho4 DNA-binding domain is capable of efficiently disrupting the nucleosome with a Pho4-binding site, whereas the complementary hybrid protein (Pho4 activation domain, GR DNA-binding domain) does not labilize the B nucleosome. Therefore, we conclude that significant activation by Pho4 requires nucleosome disruption, whereas equivalent transcriptional activation by GR is not accompanied by overt perturbation of nucleosome structure. Our results show that the DNA-binding domains of the two factors play critical roles in determining how chromatin structure is modified during promoter activation.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:sh:diva-15755 (URN)10.1074/jbc.275.12.9035 (DOI)000086507700103 ()10722753 (PubMedID)2-s2.0-0034708642 (Scopus ID)
Available from: 2012-03-07 Created: 2012-03-07 Last updated: 2017-12-07Bibliographically approved
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