The nuclear lamins function in the regulation of replication, transcription, and 
epigenetic modifications of chromatin. However, the mechanisms responsible for 
these lamin functions are poorly understood. We demonstrate that A- and B-type 
lamins form separate, but interacting, stable meshworks in the lamina and have 
different mobilities in the nucleoplasm as determined by fluorescence 
correlation spectroscopy (FCS). Silencing lamin B1 (LB1) expression dramatically 
increases the lamina meshwork size and the mobility of nucleoplasmic lamin A 
(LA). The changes in lamina mesh size are coupled to the formation of LA/C-rich 
nuclear envelope blebs deficient in LB2. Comparative genomic hybridization (CGH) 
analyses of microdissected blebs, fluorescence in situ hybridization (FISH), and 
immunofluorescence localization of modified histones demonstrate that gene-rich 
euchromatin associates with the LA/C blebs. Enrichment of hyperphosphorylated 
RNA polymerase II (Pol II) and histone marks for active transcription suggest 
that blebs are transcriptionally active. However, in vivo labeling of RNA 
indicates that transcription is decreased, suggesting that the LA/C-rich 
microenvironment induces promoter proximal stalling of Pol II. We propose that 
different lamins are organized into separate, but interacting, microdomains and 
that LB1 is essential for their organization. Our evidence suggests that the 
organization and regulation of chromatin are influenced by interconnections 
between these lamin microdomains.