BCL6 encodes a transcription factor that represses genes necessary for the terminal differentiation of lymphocytes within germinal centers, and the misregulated expression of this factor is strongly implicated in several types of B cell lymphoma. The homodimeric BTB domain of BCL6 (also known as the POZ domain) is required for the repression activity of the protein and interacts directly with the SMRT and N-CoR corepressors that are found within large multiprotein histone deacetylase-containing complexes. We have identified a 17 residue fragment from SMRT that binds to the BCL6 BTB domain, and determined the crystal structure of the complex to 2.2 A. Two SMRT fragments bind symmetrically to the BCL6 BTB homodimer and, in combination with biochemical and in vivo data, the structure provides insight into the basis of transcriptional repression by this critical B cell lymphoma protein.

To examine whether fatty acid transport is abnormal in obesity, the kinetics of [ 3 H]oleate uptake by hepatocytes, cardiac myocytes, and adipocytes from adult male Wistar (؉/؉), Zucker lean (fa/؉) and fatty (fa/fa), and Zucker diabetic fatty (ZDF) rats were studied. A tissuespecific increase in oleate uptake was found in fa/fa and ZDF adipocytes, in which the V max was increased 9-fold (p < 0.005) and 13-fold (p < 0.001), respectively. This increase greatly exceeded the 2-fold increase in the surface area of adipocytes from obese animals, and did not result from trans-stimulation secondary to increased lipolysis. Adipocyte tumor necrosis factor-␣ mRNA levels, assayed by Northern hybridization, increased in the order ؉/؉ < fa/fa < ZDF. Oleate uptake was also studied in adipocytes from 20 -24-day-old male ؉/؉, fa/؉, and fa/fa weanlings. These animals were not obese, and had equivalent plasma fatty acid and glucose levels. Tumor necrosis factor-␣ mRNA levels in ؉/؉ and fa/fa cells also were similar. Nevertheless, V max was increased 2.9-fold (p < 0.005) in fa/fa compared ؉/؉ cells. These studies indicate 1) that regulation of fatty acid uptake is tissuespecific and 2) that up-regulation of adipocyte fatty acid uptake is an early event in Zucker fa/fa rats. These findings are independent of the role of any particular fatty acid transporter. Adipocyte mRNA levels of three putative transporters, mitochondrial aspartate aminotransferase, fatty acid translocase, and fatty acid transporting protein (FATP) were also determined; mitochondrial aspartate aminotransferase and FATP mRNAs correlated strongly with fatty acid uptake.

June 19, 1987) ABSTRACT A portion of the hepatocellular uptake of nonesterified long-chain fatty acids is mediated by a specific 40-kDa plasma membrane fatty acid binding protein, which has also been isolated from the gut. To investigate whether a similar transport process exists in other tissues with high transmembrane fatty acid fluxes, initial rates (Vd) of [3H]-

The hepatic plasma membrane fatty acidbinding protein (h-FABPpM) [14C]taurocholate. The inhibition of oleate uptake produced by anti-h-FABPpM can be eliminated by preincubation of the antiserum with mGOT; similarly, the plasma membrane immunofluorescence produced by either antiserum can be elimiated by preincubation with the other antigen. These data suggest that h-FABPpM and mGOT are closely related.