Document Detail


A SUMO-regulated activation function controls synergy of c-Myb through a repressor-activator switch leading to differential p300 recruitment.
MedLine Citation:
PMID:  20385574     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Synergy between transcription factors operating together on complex promoters is a key aspect of gene activation. The ability of specific factors to synergize is restricted by sumoylation (synergy control, SC). Focusing on the haematopoietic transcription factor c-Myb, we found evidence for a strong SC linked to SUMO-conjugation in its negative regulatory domain (NRD), while AMV v-Myb has escaped this control. Mechanistic studies revealed a SUMO-dependent switch in the function of NRD. When NRD is sumoylated, the activity of c-Myb is reduced. When sumoylation is abolished, NRD switches into being activating, providing the factor with a second activation function (AF). Thus, c-Myb harbours two AFs, one that is constitutively active and one in the NRD being SUMO-regulated (SRAF). This double AF augments c-Myb synergy at compound natural promoters. A similar SUMO-dependent switch was observed in the regulatory domains of Sp3 and p53. We show that the change in synergy behaviour correlates with a SUMO-dependent differential recruitment of p300 and a corresponding local change in histone H3 and H4 acetylation. We therefore propose a general model for SUMO-mediated SC, where SUMO controls synergy by determining the number and strength of AFs associated with a promoter leading to differential chromatin signatures.
Authors:
Ann-Kristin Molvaersmyr; Thomas Saether; Siv Gilfillan; Petra Isabel Lorenzo; Heidi Kvaløy; Vilborg Matre; Odd Stokke Gabrielsen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-12
Journal Detail:
Title:  Nucleic acids research     Volume:  38     ISSN:  1362-4962     ISO Abbreviation:  Nucleic Acids Res.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-25     Completed Date:  2010-09-29     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0411011     Medline TA:  Nucleic Acids Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  4970-84     Citation Subset:  IM    
Affiliation:
Department of Molecular Biosciences, University of Oslo, Oslo, Norway.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Chromatin / metabolism
DNA / metabolism
E1A-Associated p300 Protein / metabolism*
Gene Expression Regulation
Humans
Promoter Regions, Genetic
Protein Binding
Protein Structure, Tertiary
Proto-Oncogene Proteins c-myb / chemistry,  metabolism*
Repressor Proteins / chemistry,  metabolism*
SUMO-1 Protein / metabolism*
Trans-Activators / chemistry,  metabolism*
Chemical
Reg. No./Substance:
0/Chromatin; 0/Proto-Oncogene Proteins c-myb; 0/Repressor Proteins; 0/SUMO-1 Protein; 0/Trans-Activators; 9007-49-2/DNA; EC 2.3.1.48/E1A-Associated p300 Protein
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