Gene regulatory loops at lamina-associated domains

The nuclear lamina provides a repressive chromatin environment at the nuclear periphery. However, whereas most genes in lamina-associated domains (LADs) are repressed, approximately ten percent reside in local euchromatic contexts and are expressed. How these genes are regulated and whether they are able to contact regulatory elements in LADs or outside LADs remains unclear. Here, we integrate transcriptomic, chromatin states, microscopy and publicly available enhancer-capture Hi-C data to show that expressed genes in LADs are able to connect to enhancers in LADs and inter-LADs. Our data favor a model where the spatial topology of chromatin at the nuclear lamina is compatible with transcriptional regulation in this dynamic nuclear compartment. Overall design: Using public enhancer capture Hi-C (ECHI-C) data for differentating adipocytes, we have analyzed enhancer connections in chromatin at the nuclear lamina in human primary adipose stem cells (ASCs). We have mapped lamin A/C (LMNA/C) enrichment throughout the genome by ChIP-seq of lamin AC on Day 0, 1 and 3 of in vitro adipogenic differentiation. Six histone modifications (H3K4me3, H3K4me1, H3K27ac, H3K27me3, H3K36me3, and H3K9me3) were also mapped from proliferating ASC (Pro; day minus 2 before induction of differentiation) in culture to learn chromatin states. These datasets provide a genomic context to characterize sites of chromatin (enhancer) interactions in lamina-associated domains in the adipose lineage.