fLADs

Facultative lamin-associated domains (fLADs) are regions of the genome that interact with the nuclear lamina in a cell-type–specific or condition-dependent manner. They are distinguished from constitutive LADs (cLADs), which associate with the lamina across many cell types. The defining feature of fLADs is their dynamic lamina association: a given genomic region may be lamina-associated in one cell type but not in another, or may switch during development or in response to environmental cues.

fLADs are typically identified through genome-wide mapping of lamina contacts, commonly using DamID with lamin B1 or lamin A/C chromatin immunoprecipitation, often analyzed across multiple cell types to determine which LADs are facultative. In the lamina-associated state, these regions frequently exhibit repressive chromatin features and reduced transcription, contributing to the silencing of lineage-inappropriate genes in a given cell type. They are often, but not exclusively, gene-poor and may coincide with late replication timing and compact chromatin.

Functionally, fLADs participate in the spatial organization of the genome by anchoring portions of the genome to the nuclear periphery, thereby influencing gene expression programs during development and differentiation. Their dynamic nature reflects the plasticity of nuclear architecture in response to developmental cues or environmental signals. In contrast to cLADs, which are relatively stable across cell types, fLADs highlight the context-dependent aspects of lamina-genome interactions.