Polycomb repression of Hox genes involves spatial feedback but not domain compaction or phase transition.

Polycomb group proteins have a critical role in silencing transcription during development. It is commonly proposed that Polycomb-dependent changes in genome folding, which compact chromatin, contribute directly to repression by blocking the binding of activating complexes. Recently, it has also been argued that liquid-liquid demixing of Polycomb proteins facilitates this compaction and repression by phase-separating target genes into a membraneless compartment.

Structural elements promote architectural stripe formation and facilitate ultra-long-range gene regulation at a human disease locus.

Enhancer clusters overlapping disease-associated mutations in Pierre Robin sequence (PRS) patients regulate SOX9 expression at genomic distances over 1.25 Mb. We applied optical reconstruction of chromatin architecture (ORCA) imaging to trace 3D locus topology during PRS-enhancer activation.

Analytic approaches to stochastic gene expression in multicellular systems.

Deterministic thermodynamic models of the complex systems, which control gene expression in metazoa, are helping researchers identify fundamental themes in the regulation of transcription. However, quantitative single cell studies are increasingly identifying regulatory mechanisms that control variability in expression. Such behaviors cannot be captured by deterministic models and are poorly suited to contemporary stochastic approaches that rely on continuum approximations, such as Langevin methods.

Rapid transcription fosters coordinate snail expression in the Drosophila embryo.

Transcription is commonly held to be a highly stochastic process, resulting in considerable heterogeneity of gene expression among the different cells in a population. Here, we employ quantitative in situ hybridization methods coupled with high-resolution imaging assays to measure the expression of snail, a developmental patterning gene necessary for coordinating the invagination of the mesoderm during gastrulation of the Drosophila embryo. Our measurements of steady-state mRNAs suggest that there is very little variation in snail expression across the different cells that make up the mesoderm and that synthesis approaches the kinetic limits of Pol II processivity.