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...

Phase-separated multi-molecular assemblies provide a general regulatory mechanism to compartmentalize biochemical reactions within cells. We propose that a phase separation model explains established and recently described features of transcriptional control. These features include the formation of super-enhancers, the sensitivity of super-enhancers to perturbation, the transcriptional bursting...

Cell-specific expression of many genes is conveyed by multiple enhancers, with each individual enhancer controlling a particular expression domain. In contrast, multiple enhancers drive similar expression patterns of some genes involved in embryonic development, suggesting regulatory redundancy. Work in Drosophila has indicated that functionally overlapping enhancers canalize development by buf...

Super-enhancer is a newly proposed concept, which refers to clusters of enhancers that can drive cell-typespecific gene expression and are crucial in cell identity. Many disease-associated sequence variations are enriched in the super-enhancer regions of disease-relevant cell types. Thus, super-enhancers can be used as potential biomarkers for disease diagnosis and therapeutics. Current studies...

Enhancers act over many kilobase pairs to activate target promoters, but their activity is constrained by insulator elements that prevent indiscriminate activation of nearby genes. In the July 1, 2009, issue of Genes & Development, Chopra and colleagues (pp. 1505-1509) report that promoters containing a stalled Pol II are activated by enhancers, but these promoters also serve as insulators that...

Cis-regulatory modules are non-protein-coding regions of DNA essential for the control of gene expression. One class of regulatory modules is embryonic enhancers, which drive gene expression during development as a result of transcription factor protein binding at the enhancer sequences. Recent comparative studies have begun to investigate the evolution of the sequence architecture within enhan...