ATP-dependent chromatin-remodeling complexes are known to facilitate transcriptional activation by opening chromatin structures. We report a novel human complex, named NURD, which contains not only ATP-dependent nucleosome disruption activity, but also histone deacetylase activity, which usually associates with transcriptional repression. The deacetylation is stimulated by ATP on nucleosomal templates, suggesting that nucleosome disruption aids the deacetylase to access its substrates. One subunit of NURD was identified as MTA1, a metastasis-associated protein with a region similar to the nuclear receptor core-pressor, N-CoR; and antibodies against NURD partially relieve transcriptional repression by thyroid hormone receptor. These results suggest that ATP-dependent chromatin remodeling can participate in transcriptional repression by assisting repressors in gaining access to chromatin.
The SWI͞SNF family of chromatin-remodeling complexes facilitates gene expression by helping transcription factors gain access to their targets in chromatin. SWI͞SNF and Rsc are distinctive members of this family from yeast. They have similar protein components and catalytic activities but differ in biological function. Rsc is required for cell cycle progression through mitosis, whereas SWI͞ SNF is not. Human complexes of this family have also been identified, which have often been considered related to yeast SWI͞SNF. However, all human subunits identified to date are equally similar to components of both SWI͞SNF and Rsc, leaving open the possibility that some or all of the human complexes are rather related to Rsc. Here, we present evidence that the previously identified human SWI͞SNF-B complex is indeed of the Rsc type. It contains six components conserved in both Rsc and SWI͞SNF. Importantly, it has a unique subunit, BAF180, that harbors a distinctive set of structural motifs characteristic of three components of Rsc. Of the two mammalian ATPases known to be related to those in the yeast complexes, human SWI͞SNF-B contains only the homolog that functions like Rsc during cell growth. Immunofluorescence studies with a BAF180 antibody revealed that SWI͞ SNF-B localizes at the kinetochores of chromosomes during mitosis. Our data suggest that SWI͞SNF-B and Rsc represent a novel subfamily of chromatin-remodeling complexes conserved from yeast to human, and could participate in cell division at kinetochores of mitotic chromosomes.
Flaviviruses are transmitted between bird and mammalian hosts via mosquitoes or ticks. Flaviviruses, such as dengue virus, Japanese encephalitis virus, West Nile virus (WNV), St. Louis encephalitis virus, Murray Valley virus, and tick-borne encephalitis virus, can sometimes cause severe disease in infected humans (10, 25). The genomes of flaviviruses are singlestranded, positive-polarity RNAs of approximately 11 kb and encode a single large polyprotein that is posttranslationally processed by viral and cellular proteases into three structural proteins and seven nonstructural proteins (35). During the flavivirus replication cycle, which takes place in the cytoplasm of infected cells, the genomic RNA serves as the only viral mRNA and is also the template for transcription of the complementary minus-strand RNA. The minus-strand RNA in turn serves as a template for the synthesis of genomic RNA. Plusstrand synthesis is 10 to 100 times more efficient than minusstrand synthesis (35). The noncoding regions (NCRs) of the flavivirus genome contain terminal RNA structures that are conserved between divergent flaviviruses even though only short sequences in these regions are conserved (8,9,28,37,38). The terminal RNA structures located at the 3Ј ends of the genome and complementary minus-strand RNAs differ from each other in shape and size. Deletion or mutation of either 3Ј-terminal structure in flavivirus infectious clones resulted in no progeny virus production, indicating that these regions are essential for virus replication (10a, 32, 46). However, specific cis-acting signal sequences within these structures have not yet been mapped or functionally analyzed. The WNV 3Ј-terminal RNA plus-and minus-strand structures have previously been reported to bind specifically to different sets of cell proteins (3,38).Understanding the mechanisms and components involved in the initiation and regulation of nascent viral-genome RNA synthesis from the minus-strand template is the ultimate goal of ongoing studies. The formation in solution of the 3Ј-terminal stem-loop structure of the WNV minus-strand RNA [WNV 3Ј(Ϫ) SL RNA] was previously confirmed by RNase structure probing (38). Three RNA-protein complexes (RPCs) were detected by gel shift mobility assays performed with baby hamster kidney (BHK) cytoplasmic extracts and the WNV 3Ј(Ϫ) SL RNA probe (38). The same pattern of RPCs was observed when WNV-infected or uninfected BHK S100 cytoplasmic cell extracts were used, suggesting that the proteins in these complexes were cellular proteins. UV-induced cross-linking studies indicated that the molecular masses of the RNA binding proteins in these complexes were 42, 50, 60, and 108 kDa. The specificities of these RNA-protein interactions were demonstrated by competition gel mobility shift and competition UVinduced cross-linking assays (38).
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