Functionally distinct promoter classes initiate transcription via different mechanisms reflected in focused versus dispersed initiation patterns.

Recruitment of RNA polymerase II (Pol II) to promoters is essential for transcription. Despite conflicting evidence, the Pol II preinitiation complex (PIC) is often thought to have a uniform composition and to assemble at all promoters via an identical mechanism. Here, using Drosophila melanogaster S2 cells as a model, we demonstrate that different promoter classes function via distinct PICs.

Developmental and housekeeping transcriptional programs in Drosophila require distinct chromatin remodelers.

Gene transcription is a highly regulated process in all animals. In Drosophila, two major transcriptional programs, housekeeping and developmental, have promoters with distinct regulatory compatibilities and nucleosome organization. However, it remains unclear how the differences in chromatin structure relate to the distinct regulatory properties and which chromatin remodelers are required for these programs.

Differential cofactor dependencies define distinct types of human enhancers.

All multicellular organisms rely on differential gene transcription regulated by genomic enhancers, which function through cofactors that are recruited by transcription factors. Emerging evidence suggests that not all cofactors are required at all enhancers, yet whether these observations reflect more general principles or distinct types of enhancers remained unknown. Here we categorized human enhancers by their cofactor dependencies and show that these categories provide a framework to understand the sequence and chromatin diversity of enhancers and their roles in different gene-regulatory programmes.

Differential context-specific impact of individual core promoter elements on transcriptional dynamics.

Eukaryotic transcription occurs in bursts that vary in size and frequency, but the contribution of individual core promoter elements to transcriptional bursting is not known. Here we analyze the relative contributions to bursting of the individual core promoter elements-CCAAT, TATAA-like, Sp1BS, and Inr-of an MHC class I gene in primary B-cells during both basal and activated transcription. The TATAA-like, Sp1BS, and Inr elements all function as negative regulators of transcription, and each was found to contribute differentially to the overall bursting pattern of the promoter during basal transcription.

Utility of a Phylogenetic Perspective in Structural Analysis of CYP72A Enzymes from Flowering Plants.

Plant adaptation to external pressures depends on functional diversity in cytochrome P450 (CYP) enzymes. CYPs contain structural domains necessary for the characteristic P450 fold that allows monooxygenation, but they also have great variation in substrate binding affinity. Plant genomes typically contain hundreds of CYPs that contribute to essential functions and species-specific metabolism.

Computational tools and algorithms for designing customized synthetic genes.

Advances in DNA synthesis have enabled the construction of artificial genes, gene circuits, and genomes of bacterial scale. Freedom in de novo design of synthetic constructs provides significant power in studying the impact of mutations in sequence features, and verifying hypotheses on the functional information that is encoded in nucleic and amino acids. To aid this goal, a large number of software tools of variable sophistication have been implemented, enabling the design of synthetic genes for sequence optimization based on rationally defined properties.