In addition to coding for proteins, exons can also impact transcription by encoding regulatory elements such as enhancers. It has been debated whether such features confer heightened selective constraint, or evolve neutrally. We have addressed this question by developing a new approach to disentangle the sources of selection acting on exonic enhancers, in which we model the evolutionary rates o...

Developmental programs are controlled by transcription factors and chromatin regulators, which maintain specific gene expression programs through epigenetic modification of the genome. These regulatory events at enhancers contribute to the specific gene expression programs that determine cell state and the potential for differentiation into new cell types. Although enhancer elements are known t...

Histone acetyltransferase (HAT) complexes are coactivators that are important for transcriptional activation by modifying chromatin. Metazoan SAGA and ATAC are distinct multisubunits complexes that share the same catalytic HAT subunit (GCN5 or PCAF). Here, we show that these human HAT complexes are targeted to different genomic loci representing functionally distinct regulatory elements both at...

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Transcription factors bind low-affinity DNA sequences for only short durations. It is not clear how brief, low-affinity interactions can drive efficient transcription. Here, we report that the transcription factor Ultrabithorax (Ubx) utilizes low-affinity binding sites in the Drosophila melanogaster shavenbaby (svb) locus and related enhancers in nuclear microenvironments of high Ubx concentrat...

In addition to coding for proteins, exons can also impact transcription by encoding regulatory elements such as enhancers. It has been debated whether such features confer heightened selective constraint, or evolve neutrally. We have addressed this question by developing a new approach to disentangle the sources of selection acting on exonic enhancers, in which we model the evolutionary rates o...

Regulatory DNAs serve as templates to bring weakly interacting transcription factors into close proximity so they can work synergistically to switch genes on and off in time and space. Most of these regulatory DNAs are enhancers that can work over long distances--a million base pairs or more in mammals--to control gene expression. Critical enhancers are sometimes even found within the introns o...

The embryonic vertebrate heart tube develops an atrioventricular canal that divides the atrial and ventricular chambers, forms atrioventricular conduction tissue and organizes valve development. Here we assess the transcriptional mechanism underlying this localized differentiation process. We show that atrioventricular canal-specific enhancers are GATA-binding site-dependent and act as switches...