A sequence element located immediately upstream of the TATA element, and having the consensus sequence 5-G/C-G/C-G/A-C-G-C-C-3, affects the ability of transcription factor IIB to enter transcription complexes and support transcription initiation. The sequence element is recognized directly by the transcription factor IIB. Recognition involves ␣-helices 4 and 5 of IIB, which comprise a helix-turn-helix DNA-binding motif. These observations establish that transcription initiation involves a fourth core promoter element, the IIB recognition element (BRE), in addition to the TATA element, the initiator element, and the downstream promoter element, and involves a second sequence-specific general transcription factor, IIB, in addition to transcription factor IID. Efficient transcription initiation at a human protein-encoding gene requires assembly on promoter DNA of a multiprotein complex containing RNA polymerase II (Pol II) and six general transcription factors, IIA, IIB, IID, IIE, IIF, and IIH (for review, see Orphanides et al. 1996;Roeder 1996;Nikolov and Burley 1997). Previous work establishes that assembly of the complex involves three core promoter elements: (1) the TATA element, located near position −30, (2) the initiator element, located near position −1, and (3) the downstream promoter element, located near position +30 (Burke and Kadonaga 1996;Orphanides et al. 1996;Roeder 1996). Transcription factor IID is responsible for recognition of at least two of these elements. One subunit of IID, TATA-binding protein (TBP), is responsible for recognition of the TATA element; one or more of the remaining subunits of IID, TBP-associated factors (TAFs), is responsible for recognition of the downstream promoter element. It is not clear which factor is responsible for recognition of the initiator element.The crystallographic structure of a ternary complex of transcription factor IIB core domain (IIBc), TBP core domain (TBPc), and a 16-bp DNA fragment containing the TATA element shows that IIBc interacts with both TBPc and DNA, interacting with the DNA major groove immediately upstream of the TATA element and the DNA minor groove immediately downstream of the TATA element ( Fig. 1; Nikolov et al. 1995). In the crystallographic structure, details of the interaction between IIBc and the DNA major groove upstream of the TATA element are incomplete, since the structure was determined using a DNA fragment containing only three nucleotide pairs upstream of the TATA element (Nikolov et al. 1995). However, DNA-binding and site-specific protein-DNA photocross-linking experiments confirm that interaction between IIB and the DNA major groove upstream of the TATA element occurs and indicate that the interaction is extensive, spanning up to 7-9 nucleotide pairs (Lee and Hahn 1995;Lagrange et al. 1996). The observation that IIB makes extensive interactions with the DNA major groove upstream of the TATA element raises the possibility that the ability of IIB to enter into transcription complexes and, thus, the ability of IIB to support...

STAT6 plays a prominent role in adaptive immunity by transducing signals from extracellular cytokines. We now show that STAT6 is required for innate immune signaling in response to virus infection. Viruses or cytoplasmic nucleic acids trigger STING (also named MITA/ERIS) to recruit STAT6 to the endoplasmic reticulum, leading to STAT6 phosphorylation on Ser(407) by TBK1 and Tyr(641), independent of JAKs. Phosphorylated STAT6 then dimerizes and translocates to the nucleus to induce specific target genes responsible for immune cell homing. Virus-induced STAT6 activation is detected in all cell-types tested, in contrast to the cell-type specific role of STAT6 in cytokine signaling, and Stat6(-/-) mice are susceptible to virus infection. Thus, STAT6 mediates immune signaling in response to both cytokines at the plasma membrane, and virus infection at the endoplasmic reticulum.

Type I interferons (IFN) are well studied cytokines with anti-viral and immune-modulating functions. Type I IFNs are produced following viral infections, but until recently, the mechanisms of viral recognition leading to IFN production were largely unknown. Toll like receptors (TLRs) have emerged as key transducers of type I IFN during viral infections by recognizing various viral components. Furthermore, much progress has been made in defining the signaling pathways downstream of TLRs for type I IFN production. TLR7 and TLR9 have become apparent as universally important in inducing type I IFN during infection with most viruses, particularly by plasmacytoid dendritic cells. New intracellular viral pattern recognition receptors leading to type I IFN production have been identified. Many bacteria can also induce the up-regulation of these cytokines. Interestingly, recent studies have found a detrimental effect on host cells if type I IFN is produced during infection with the intracellular gram-positive bacterial pathogen, Listeria monocytogenes. This review will discuss the recent advances made in defining the signaling pathways leading to type I IFN production.

The Escherichia coil RNA polymerase oL-subunit binds through its carboxy-terminal domain (o~CTD) to a recognition element, the upstream (UP) element, in certain promoters. We used genetic and biochemical techniques to identify the residues in aCTD important for UP-element-dependent transcription and DNA binding. These residues occur in two regions of oLCTD, close to but distinct from, residues important for interactions with certain transcription activators. We used NMR spectroscopy to determine the secondary structure of ,vCTD. aCTD contains a nonstandard helix followed by four c~-helices. The two regions of ~CTD important for DNA binding correspond to the first a-helix and the loop between the third and fourth oL-helices. The o~CTD DNA-binding domain architecture is unlike any DNA-binding architecture identified to date, and we propose that aCTD has a novel mode of interaction with DNA. Our results suggest models for c~CTD-DNA and c~CTD-DNA-activator interactions during transcription initiation.