Conserved motifs in Fos and Jun define a new class of activation domain.
Fos and Jun form a tight heterodimeric complex that activates transcription by AP1 sites. We have recognized that two adjacent regions of the Jun A1 activation domain are conserved in the Fos protein, and we refer to these two homologous regions as homology box 1 (HOB1) and homology box 2 (HOB2). Using GAL4 chimeras, we show that the HOB1/HOB2 region of Fos and Jun is an independent activation domain in which HOB1 and HOB2 act cooperatively to activate transcription. This cooperativity is retained after the replacement of Fos HOB1 or HOB2 with the equivalent domain of Jun or when duplicated HOB1/HOB1 and HOB2/HOB2 combinations are generated. In the Fos protein, HOB1 or HOB2 can also cooperate with a distinct domain at the carboxyl terminus of the protein. Using the HOB2 consensus sequence as a guide, we identified a HOB2-containing activation domain in the CCAAT/enhancer binding protein (C/EBP) protein. This HOB2 motif can cooperate with as yet undefined sequences in C/EBP and will function even when linked to Jun HOB1. Thus, HOB1 and HOB2 represent inert "cooperating modules" that are combined to generate a functional activation domain. Each of these modules has the potential to cooperate with both distinct and identical domains. The presence of HOB-like modules in three different transcription factors indicates that the HOB motifs characterize a new class of activation domain. These motifs can be used now to identify other transcription factors with such modular characteristics.
Sutherland
J A
JA
Wellcome/CRC Institute, University of Cambridge, UK.
Cook
A
A
Bannister
A J
AJ
Kouzarides
T
T
D000595:Amino Acid Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D002461:Cell Line, Transformed; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors