B-cell-specific Coactivator OCA-B: Biochemical Aspects, Role in B-Cell Development and Beyond

Regulation of transcription initiation on eukaryoticclass II (protein-coding) genes is effected by activatorsthat bind to distal regulatory elements and act throughcomponents of the basal transcription machinery. Thebasal transcription machinery consists of RNA polymerase II (Pol II) and an array of general initiation factors(TFIIA, -B, -D, -E, -F, and -H) and has an intrinsic abilityto interact productively with core promoter elements thatinclude TATA motifs and sequences flanking the transcription initiation sites (for review, see Roeder 1991,1996). Such interactions, however, are highly limiting invivo due to constraints imposed, for example, by nucleosome structure, general negative cofactors, and limitingconcentrations of general initiation factors. The role of theDNA-bound activators, therefore, is to increase productive interactions of the basal transcription machinery.Many documented direct physical interactions betweenactivators and components of the basal transcription machinery would appear to provide a simple mechanism fortranscriptional activation (for review, see Koh et al. 1998;Ptashne and Gann 1990). These interactions, however, donot suffice for high levels of activator-induced transcription in a defined reconstituted cell-free system. Indeed,further studies have revealed that functional interactionsbetween activators and the basal transcription machineryare greatly facilitated through an emerging number of cofactors, leading to more physiological levels of activatorinduced transcription (see, e.g., Kaiser and Meisternst1996; Verrijzer and Tjian 1996; Roeder 1998). These cofactors are essential either for the activator function per seor for an enhancement of the inductive effects of activators, in some cases by lowering the basal (activator-independent) activities. The most noteworthy of the cofactorsare (1) TATA-binding protein (TBP) associated factors(TAFs) in TFIID; (2) positive cofactors (PCs) and negative cofactors (NCs) within the human upstream stimulatory activity (USA) fraction; (3) RNA Pol II holoenzymederived mediator components that reversibly interact withPol II; (4) coactivators that are initially associated with, orrecruited to the promoter by, DNA-bound activators, and(5) a subset of coactivators, including some in the abovementioned groups, possessing histone acetyltransferase(HAT) and ATP-dependent nucleosome remodeling activities. Cofactors in the latter group are thought to makepromoter elements within nucleosomes more accessible tothe transcription machinery (for review, see Workman andKingston 1998), whereas other cofactors are thought toact, more directly, as adapters between DNA-bound activators and components of the general transcription machinery (for review, see Roeder 1998)...