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41 Oct-1 and Oct-2: Differential Transcriptional Regulation by Proteins That Bind to the Same DNA Sequence

Winship Herr


The human POU-homeodomain proteins Oct-1 and Oct-2 can activate transcription from different promoters even though they recognize the same cis-regulatory element, the octamer motif ATGCAAAT. Studies reveal two mechanisms by which this differential transcriptional regulation is achieved. In one case, Oct-1 and Oct-2 possess promoter-selective activation domains that result in preferential activation of RNA polymerase II transcription from a small nuclear RNA promoter by Oct-1 and an mRNA promoter by Oct-2. In the other case, selective association of Oct-1 with the herpes simplex virus activator VP16 results in recruitment of Oct-1, but not Oct-2, to a new cis-regulatory site that, in the absence of VP16, is not recognized effectively by either Oct-1 or Oct-2.

One of the surprises arising from the study of transcriptional regulation in multicellular organisms has been the frequent occurrence of multiple regulatory proteins recognizing the same cis-acting DNA element. Little is known about how proteins that display the same DNA-binding activity can selectively modulate the levels of transcription from different promoters. In this chapter, I describe two modes by which such differential transcriptional regulation is achieved, as illustrated by studies of the homeodomain proteins Oct-1 and Oct-2, two proteins that bind to an 8- bp ATGCAAAT octamer sequence found in a variety of promoters. First, particular activation domains can selectively activate different promoters even when attached to an identical DNA-binding domain. Second, through selective interaction with an auxiliary protein, one of the two proteins can be recruited to a new cis-regulatory binding site. The...

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