Details

Autor(en) / Beteiligte

• Carey, Michael

Titel

The Enhanceosome and Transcriptional Synergy

Ist Teil von

• Cell, 1998-01, Vol.92 (1), p.5-8

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

1998

Quelle

MEDLINE

Beschreibungen/Notizen

• Development of a complex eukaryote requires the differential transcription of over 50,000 genes in precise spatial and temporal patterns. One of the key problems in the gene expression field is understanding how an organism can achieve such diversity, while maintaining cell specificity and responding dynamically to its environment. One solution is to employ a limited repertoire of activators to minimize the complexity necessary to link related signaling pathways and to integrate diverse regulatory cues. The current view is that the cell accomplishes this by employing the principles of cooperativity and transcriptional synergy, where small combinations of ubiquitous, signal- and tissue-specific activators can be used to execute an exponentially larger number of regulatory decisions. Thus, an RNA polymerase II (pol II) enhancer responds to signals by organizing unique combinations of activators in a tightly clustered pattern that promotes their interaction and cooperative binding to DNA. The pol II transcriptional machinery, in turn, is designed to respond in a greater-than-additive or synergistic fashion only to multiple activators. Previous studies from the Maniatis and Grosschedl laboratories on the IFN beta and TCR alpha gene enhancers, respectively, provided important biochemical details of how enhancer organization and cooperativity functioned to assemble activators into a nucleoprotein complex called the "enhanceosome." A key unanswered question was "how does the enhanceosome stimulate synergistic transcription and is the precise stereo-specific arrangement of activation domains necessary for the effect?" Recent biochemical studies reporting enhanceosome-activated transcription in vitro and the identification of activator "targets" within the transcriptional machinery suggest that specific interaction surfaces are involved in synergy, and reveal new aspects of this regulation.