Sequence-specific DNA binding of the B-cell-specific coactivator OCA-B.
B-cell-specific transcription of immunoglobulin genes is mediated by the interaction of a POU domain containing transcription factor Oct-1 or Oct-2, with the B-cell-specific coactivator OCA-B (Bob-1, OBF-1) and a prototype octamer element. We find that OCA-B binds DNA directly in the major groove between the two subdomains of the POU domain, requiring both an A at the fifth position of the octamer element and contact with the POU domain. An amino-terminal fragment of OCA-B binds the octamer site in the absence of a POU domain with the same sequence specificity. Coactivator OCA-B may undergo a POU-dependent conformational change that exposes its amino terminus, allowing it to recognize specific DNA sequences in the major groove within the binding site for Oct-1 or Oct-2. The recognition of both the POU domain and the octamer sequence by OCA-B provides a mechanism for differential regulation of octamer sites containing genes by the ubiquitous factor Oct-1.
Cepek
K L
KL
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA.
Chasman
D I
DI
Sharp
P A
PA
D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002474:Cell-Free System; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism*; D051863:Host Cell Factor C1; D006801:Humans; D046911:Macromolecular Substances; D008958:Models, Molecular; D050811:Octamer Transcription Factor-1; D011401:Promoter Regions, Genetic; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000737:chemistry* / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; D018398:Homeodomain Proteins; D051863:Host Cell Factor C1; D046911:Macromolecular Substances; D050811:Octamer Transcription Factor-1; C091546:POU2AF1 protein, human; C494165:POU2F1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors