A Small Region in HMG I(Y) Is Critical for Cooperation with NF-κB on DNA

Domain Architecture of a High Mobility Group A-type Bacterial Transcriptional Factor

“…Although we have been unable to provide additional experimental evidence for this, protein-protein interactions between different HMGA molecules or of HMGA with other protein molecules have been invoked to explain the highly cooperative enhanceosome assembly (13,26,46,47,56,62). The inherent difficulty in pinpointing the mechanism of HMGA cooperativity has been noted before and attributed to, among others, its lack of defined structure (56). The latter imposes technical challenges which would also apply to CD-(183-316), and to this segment in CarD.…”

“…Thus CarD and CD-(183-316), like HMGA1a, exhibit minor groove DNA binding specificity. For the same solution conditions HMGA1a binds to IRE with a K D Ϸ 40 nM (56). As judged by the concentrations of CarD and CD-(183-316) required for EMSA analysis, the specific DNA binding affinity for the acidic AT-hook fragment of CarD is slightly lower than for HMGA1a, whereas it may be as much as an order of magnitude weaker for CarD (Fig.…”

High-Mobility-Group Protein I Can Modulate Binding of Transcription Factors to the U5 Region of the Human Immunodeficiency Virus Type 1 Proviral Promoter

“…HMG I/Y can directly interact via protein-protein interactions, employing different interaction surfaces, with a number of different transcriptional activators, including NF-B (42,50,51), ATF-2 (13), SRF (8), NF-Y (10), Oct 2A (1), Elf (24), and c-Rel (22), increasing their affinity for DNA. Typically, target genes for this HMG I/Y enhancement of factor binding are inducible and include genes for cytokines such as beta interferon (42), interleukin-2 receptor ␣ chain (24), E-selectin (30), interleukin-2, and macrophage colony-stimulating factor (22).…”

“…For the beta interferon promoter, higher-order transcription factor complex formation can be further stabilized by HMG I/Yfactor interactions (14). Paradoxically, in the case of NF-B, the protein-interacting domain of HMG I/Y includes part of the same domain that interacts with DNA (51). The biological importance of HMG I/Y in regulating gene expression is further implied by the finding that the expression of HMG I/Y is upregulated in rapidly proliferating cells, including early embryonic cells (7) and neoplastic tissues (19,25).…”

“…HMG I/Y is characterized by three tandemly organized basic DNA-binding modules separated by a flexible linker; each individual module is capable of interacting with the minor groove of DNA in a structurally specific manner, with the second basic repeat being responsible for high-affinity binding (4,18,49,51). These consensus basic repeats adopt a defined crescentshaped planar structure, resembling the drugs netropsin and distamycin (6).…”