As a class of cis-regulatory elements, enhancers were first identified as the genomic regions that are able to markedly increase the transcription of genes nearly 30years ago. Enhancers can regulate gene expression in a cell-type specific and developmental stage specific manner. Although experimental technologies have been developed to identify enhancers genome-wide, the design principle of the...

Sequence variation within enhancers plays a major role in both evolution and disease, yet its functional impact on transcription factor (TF) occupancy and enhancer activity remains poorly understood. Here, we assayed the binding of five essential TFs over multiple stages of embryogenesis in two distant Drosophila species (with 1.4 substitutions per neutral site), identifying thousands of orthol...

Enhancers, as specialized genomic cis-regulatory elements, activate transcription of their target genes and play an important role in pathogenesis of many human complex diseases. Despite recent systematic identification of them in the human genome, currently there is an urgent need for comprehensive annotation databases of human enhancers with a focus on their disease connections. In response, ...

Gene expression is precisely controlled in time and space through the integration of signals that act at gene promoters and gene-distal enhancers. Classically, promoters and enhancers are considered separate classes of regulatory elements, often distinguished by histone modifications. However, recent studies have revealed broad similarities between enhancers and promoters, blurring the distinct...

A series of basic carboxamides of actagardine (1), a lantibiotic possessing good antistreptococcal activity, were synthetized. Some physico-chemical characteristics, in particular charge and lipophilicity, that influence water solubility were determined. The in vitro and in vivo activity was evaluated. The monocarboxamides were generally more active than actagardine against selected Gram-positi...

Executive Summary The search for treatments for dementia, alongside other scientific and societal changes, has prompted the development of symptomatic treatments and disease-modifying drugs for people with degenerative brain diseases, mild cognitive impairment, and psychiatric diseases that involve cognition impairment. The enhancement of aspects of cognition, such as learning and memory, now s...

Transcriptional enhancers integrate the contributions of multiple classes of transcription factors (TFs) to orchestrate the myriad spatio-temporal gene expression programs that occur during development. A molecular understanding of enhancers with similar activities requires the identification of both their unique and their shared sequence features. To address this problem, we combined phylogene...