We have developed a new DNA microarray-based technology, termed protein binding microarrays (PBMs), that allows rapid, high-throughput characterization of the in vitro DNA binding site sequence specificities of transcription factors in a single day. Using PBMs, we identified the DNA binding site sequence specificities of the yeast transcription factors Abf1, Rap1, and Mig1. Comparison of these proteins' in vitro binding sites versus their in vivo binding sites indicates that PBM-derived sequence specificities can accurately reflect in vivo DNA sequence specificities. In addition to previously identified targets, Abf1, Rap1, and Mig1 bound to 107, 90, and 75 putative new target intergenic regions, respectively, many of which were upstream of previously uncharacterized open reading frames (ORFs). Comparative sequence analysis indicates that many of these newly identified sites are highly conserved across five sequenced sensu stricto yeast species and thus are likely to be functional in vivo binding sites that potentially are utilized in a conditionspecific manner. Similar PBM experiments will likely be useful in identifying novel cis regulatory elements and transcriptional regulatory networks in various genomes.The interactions between transcription factors (TFs) and their DNA binding sites are an integral part of transcriptional regulatory networks. They control the coordinated expression of thousands of genes during normal growth and in response to external stimuli. Significant progress has been made recently in the accumulation and analysis of mRNA transcript Correspondence should be addressed to M.L.B.

We propose a general strategy to develop accurate Force Fields (FF) for metallic systems derived from ab initio quantum mechanical (QM) calculations; we illustrate this approach for tantalum. As input data to the FF we use the linearized augmented plane wave method (LAPW) with the generalized gradient approximation (GGA) to calculate: (i) the zero temperature equation of state (EOS) of Ta for bcc, fcc, and hcp crystal structures for pressures up to ∼ 500 GPa. (ii) Elastic constants. (iii) We use a mixed-basis pseudopotential code to calculate volume relaxed vacancy formation energy also as a function of pressure. In developing the Ta FF we also use previous QM calculations of: (iv) the equation of state for the A15 structure.(v) the surface energy bcc (100). (vi) energetics for shear twinning of the bcc crystal. We find that with appropriate parameters an embedded atom model force field (denoted as qEAM FF) is able to reproduce all this QM data. Thus, the same FF describes with good accuracy the bcc, fcc, hcp and A15 phases of Ta for pressures from ∼ −10 GPa to ∼ 500 GPa, while also describing the vacancy, surface energy, and shear transformations. The ability of this single FF to describe such a range of systems with a variety of coordinations suggests that it would be accurate for describing defects such as dislocations, grain boundaries, etc. We illustrate the use of the qEAM FF with molecular dynamics to calculate such finite temperature properties as the melting curve up to 300 GPa; we obtain a zero pressure melting temperature of T melt = 3150 ± 50 K in good agreement with experiment (3213 − 3287 K). We also report on the thermal expansion of Ta in a wide temperature range; our calculated thermal expansivity agrees well with experimental data.