Recruitment of Gcn5-containing complexes during c-Myc-dependent gene activation. Structure and function aspects.
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 (i) 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.
Flinn
Elizabeth M
EM
Section for Natural Sciences, Södertörns Högskola, Box 4101, Huddinge 141 04, Sweden.
Wallberg
Annika E
AE
Hermann
Stefan
S
Grant
Patrick A
PA
Workman
Jerry L
JL
Wright
Anthony P H
AP
D018797:Cell Cycle Proteins; D002843:Chromatin / Q000737:chemistry; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases; D010446:Peptide Fragments / Q000502:physiology; D028061:Phosphate Transport Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000502:physiology*; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000032:analysis*; D014157:Transcription Factors; D015533:Transcriptional Activation; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D018797:Cell Cycle Proteins; D002843:Chromatin; D051548:Histone Acetyltransferases; D010446:Peptide Fragments; D028061:Phosphate Transport Proteins; D016271:Proto-Oncogene Proteins c-myc; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C055831:phosphate permease