Book of Abstracts: Albany 2003
June 17-21 2003
Structural Aspects of Gene Expression by Formation of High Order Protein Complexes on Promoter DNA: A Recent Progress
Assembly of stereospecific, multiprotein complexes on enhancers and promoters is a key step in transcriptional activation and tightly controlled by sequence specific transcriptional regulatory factors. Physical interactions between these transcriptional regulatory factors are supposed to control their DNA bindings which lead to synergistic activation of transcription. Recent X-ray diffraction studies confirmed three possible modes of cooperative promoter DNA binding by two transcriptional regulatory factors. One of the best characterized modes is a cooperative binding of transcriptional regulatory factors to adjacent sites on promoter DNA (e.g. NFAT-Fos-Jun-DNA, MATα2-MCM1-DNA, MATα2-MATa1-DNA, NF-κB p50-p65-DNA, Ubx-Exd-DNA, Ets-1-Pax-5-DNA and PU.1-IRF-4-DNA complexes). Another mode of cooperative DNA recognition involves the binding of two transcriptional regulatory factors to a single site on promoter DNA, where one transcriptional regulatory factor interacts with DNA while another one enhances the DNA binding affinity of complex without interacting with DNA (e.g. GABPα-GABPβ-DNA and AML1-CBFβ-DNA complexes). And the third mode of cooperation involves the recognition of two widely separated sites of promoter DNA where the cooperation of interacting proteins is accompanied by looping of intervening portion of DNA (e.g. c-Myb-C/EBPβ-DNA and c-Myb-C/EBPα-DNA complexes). The structural studies reveal that the disease related mutations often mapped to protein-protein and/or protein-DNA interaction interfaces of transcription regulatory factors thus preventing their cooperative DNA binding.
Tahir H. Tahirov