LADs in Gene Regulation
The genome is organised at two levels, structurally, by folding into many discrete units called topologically-associated domains (TADs) and spatially, by attaching a sub-set of transcriptionally inactive TADs to the nuclear envelope in so called lamina-associated domains (LADs). While TADs control transcription by isolating regulatory sequences specifically with their target promoters, it remains unclear what function spatial compartmentalisation in LADs plays in developmental gene regulation and disease.
To address this, we utilise variations of CRISPR/Cas9 and in vitro and in vivo model systems to perturb and alter LADs and analyse the consequences for differentiation, development and gene regulation. However, through state-of-the-art technologies such as Chromosome Conformation Capture, DamID-seq and enhancer assays, we then further examine the wider effects of LAD disruption on enhancer activity, chromatin structure, 3D nuclear organisation.
Together, this approach allows us to examine the fundamental mechanisms of higher order genome organisation and its role in regulating gene expression and development.