Abstract
OCA-B is a B-cell-specific coregulator of the broadly expressed POU domain transcription factor Oct-1. OCA-B associates with the Oct-1 POU domain, a bipartite DNA-binding structure containing a POU-specific (POU[S]) domain joined by a flexible linker to a POU homeodomain (POU[H]). Here, we show that OCA-B alters the activity of Oct-1 in two ways. It provides a transcriptional activation domain which, unlike Oct-1, activates an mRNA-type promoter effectively, and it stabilizes Oct-1 on the Oct-1-responsive octamer sequence ATGCAAAT. These properties of OCA-B parallel those displayed by the herpes simplex virus Oct-1 coregulator VP16. OCA-B, however, interacts with a different surface of the DNA-bound Oct-1 POU domain, interacting with both the POU(S) and POU(H) domains and the center of the ATGCAAAT octamer sequence. The OCA-B and VP16 interactions with the Oct-1 POU domain are sufficiently different to permit OCA-B and VP16 to bind the Oct-1 POU domain simultaneously. These results emphasize the structural versatility of the Oct-1 POU domain in its interaction with coregulators.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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B-Lymphocytes / metabolism
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Base Sequence
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Binding Sites / genetics
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DNA / genetics
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DNA / metabolism
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DNA Primers / genetics
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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HeLa Cells
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Herpes Simplex Virus Protein Vmw65 / genetics
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Herpes Simplex Virus Protein Vmw65 / metabolism*
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Host Cell Factor C1
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Humans
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In Vitro Techniques
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Models, Molecular
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Octamer Transcription Factor-1
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Polymerase Chain Reaction
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Promoter Regions, Genetic
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Protein Conformation
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RNA, Messenger / genetics
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Trans-Activators / chemistry
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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DNA Primers
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DNA-Binding Proteins
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HCFC1 protein, human
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Herpes Simplex Virus Protein Vmw65
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Host Cell Factor C1
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Octamer Transcription Factor-1
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POU2AF1 protein, human
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POU2F1 protein, human
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RNA, Messenger
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SNAPC protein complex, human
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Trans-Activators
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Transcription Factors
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DNA