Enhancers are DNA regulatory elements that control gene transcription. During development, different sets of enhancers drive the changes in gene expression that underlie cell fate. We seek to understand the mechanisms controlling where and when enhancers are used. In particular, we focus on the mechanisms controlling physical access to enhancer DNA in chromatin. In vivo, DNA is packaged into nucleosomes, the repeating unit of chromatin. Generally-speaking, nucleosomes are barriers to transcription factor binding. As a result, nucleosome-occupied enhancers (ie. “closed chromatin”) are inaccessible to transcription factors and inactive. By contrast, nucleosome-depleted DNA (ie. “open chromatin”) is generally permissive to transcription factor binding. Hence, regulating the accessibility of enhancers is a fundamental step in control their activity.

What are the factors that open chromatin?

What are the factors that close chromatin?

What co-regulators are involved?

How are spatial and temporal regulatory cues integrated?

We employ a combination of approaches to answer these questions, including a range of genomics assays (ATAC-seq/FAIRE-seq, CUT&RUN/ChIP-seq, RNA-seq), Drosophila genetics, CRISPR, microscopy, and biochemistry.

Dynamic open chromatin sites correspond to functional enhancers. (top) Browser shot of FAIRE-seq data from three stages of embryogenesis. Open chromatin profiles are temporally dynamic. (bottom) Confocal image of an enhancer cloned from the prd gene locus based on FAIRE-seq data. Enhancer activity is shown in green.