An atlas of lamina-associated chromatin across twelve human cell types reveals an intermediate chromatin subtype

Three-dimensional genome organization, specifically organization of chromatin at the nuclear periphery, coordinates cell type-specific gene regulation and is critical for maintenance of cell type identity. While various histone modifications and chromatin-associated proteins have provided important insights into genome organization, nuclear peripheral chromatin maps have only been generated in a few cell types. In this study, we define nuclear peripheral chromatin organization signatures based on association with LAMIN-B1 and/or the histone modification H3K9me2 across thirteen human cell types encompassing undifferentiated stem cells and intermediate and terminally differentiated cells from all three germ layers. Genomic analyses across these thirteen human cell types reveal sub-compartmentalization of peripheral heterochromatin, specifically two subtypes of LAMIN B1-associated chromatin, which appear to be physically and functionally distinct. By integrating peripheral chromatin maps with transcriptional data, we find evidence of cooperative shifts between chromatin structure and gene expression associated with each cell type. Across multiple, distinct cell cell types, this work revealed that lamina-associated chromatin is organized into at least two fundamentally different compartments, with diverse genome coverage, characteristics and gene complements, underscoring the complexity of peripheral chromatin organization. Moreover, these maps encompass an atlas of peripheral chromatin and associated features in multiple human cell types from all three germ layers, providing the largest resource to date for peripheral chromatin organization and a greater appreciation for how this organization may impact the establishment and maintenance of cellular identity.