CHURCHMAN LAB

From the nucleus to mitochondria, we study the many layers of gene regulation.

We seek an integrative view of gene regulation to understand where, when and how genes are controlled.

We apply experimental and computational approaches that probe the many steps of gene expression, from transcription to translation.

Recent highlights

RNA flow analysis

How does RNA flow through the cell? From their synthesis, chromatin release, nuclear export, ribosome engagement, and eventual degradation, we quantified the lives of human transcripts genome-wide.

Single-molecule views of transcription and chromatin

We used long-read chromatin fiber sequencing (Fiber-seq) to visualize RNA polymerases within their native chromatin context at single-molecule and near single-nucleotide resolution along up to 30 kb fibers. We found pervasive direct coordination and anti-coordination between nearby Pol II genes, Pol III genes, transcribed enhancers, and insulator elements. This coordination was limited spatially and depended on whether insulators were simultaneously bound to the same DNA molecule.

Using mitochondrial Fiber-seq, we observed how mitochondrial DNA is packaged with single molecule resolution. We found that, unlike the nuclear genome, human mtDNA largely undergoes all-or-none global compaction, with most nucleoids existing in an inaccessible, inactive state. The primary nucleoid-associated protein TFAM directly modulates the fraction of inaccessible nucleoids both in vivo and in vitro, acting consistently with a nucleation-and-spreading mechanism to coat and compact mitochondrial nucleoids.