The nuclear lamina contributes to defining the shape and functions of the nucleus. Both A- and B-type lamins make contacts with the genome through large chromatin-associated domains (LADs) [Kind and van Steensel, 2010]. LADs include intergenic regions and mostly, but not exclusively, repressed genes. We show by chromatin immunoprecipitation (ChIP) and promoter array hybridization that in adipocyte progenitor cells, lamin A interacts with over 4000 promoters linked to genes involved in signaling and differentiation [Lund et al. 2013]. Most lamin A-bound loci cluster non-randomly into lamin-rich domains which we assimilate to LADs; a substantial number also localize outside LADs as stand-alone loci. Lamin-interacting loci are found both at the nuclear periphery and in the nuclear interior. Within promoter regions, lamin A contacts spatially restricted sub-domains that correlate with distinct transcriptional outcomes in a manner dependent on associated chromatin marks. Down-regulation of lamin A does not elicit activation of promoters that disengage from lamin A despite a large genomic increase in H3K4 trimethylation. Adipogenic differentiation remodels lamin-promoter contacts at the genome-wide and sub-promoter levels. Notably, genes controlling adipogenic differentiation disengage from lamin A, acquire H3K4me3 and become activated, while genes involved in non-adipogenic lineages or pluripotency retain lamin A and remain silent. Our results suggest that lamin A modulates gene expression through interaction with adjustable domains on promoters. We propose a model of differentiation-driven lineage-specific unlocking of genes from the nuclear lamina before transcriptional activation. The recent development of an algorithm for the detection of low-level genomic enrichment in lamins or other nuclear envelope proteins by ChIP-seq is expected to unveil new insights on the significance of lamin-genome interactions.