PMID- 19141474 OWN - NLM STAT- MEDLINE DCOM- 20090203 LR - 20220309 IS - 0890-9369 (Print) IS - 1549-5477 (Electronic) IS - 0890-9369 (Linking) VI - 22 IP - 24 DP - 2008 Dec 15 TI - The A- and B-type nuclear lamin networks: microdomains involved in chromatin organization and transcription. PG - 3409-21 LID - 10.1101/gad.1735208 [doi] AB - 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. FAU - Shimi, Takeshi AU - Shimi T AD - Department of Cell and Molecular Biology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA. FAU - Pfleghaar, Katrin AU - Pfleghaar K FAU - Kojima, Shin-ichiro AU - Kojima S FAU - Pack, Chan-Gi AU - Pack CG FAU - Solovei, Irina AU - Solovei I FAU - Goldman, Anne E AU - Goldman AE FAU - Adam, Stephen A AU - Adam SA FAU - Shumaker, Dale K AU - Shumaker DK FAU - Kinjo, Masataka AU - Kinjo M FAU - Cremer, Thomas AU - Cremer T FAU - Goldman, Robert D AU - Goldman RD LA - eng GR - R01 AG023776/AG/NIA NIH HHS/United States GR - R01 CA031760/CA/NCI NIH HHS/United States GR - R01CA31760/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Genes Dev JT - Genes & development JID - 8711660 RN - 0 (CKAP2 protein, human) RN - 0 (Chromatin) RN - 0 (Cytoskeletal Proteins) RN - 0 (LMNA protein, human) RN - 0 (Lamin Type A) RN - EC 2.7.7.7 (DNA Polymerase II) SB - IM CIN - Nat Rev Mol Cell Biol. 2012 Mar;13(3):140. PMID: 22334141 MH - Chromatin/*genetics/*metabolism MH - Cytoskeletal Proteins/*genetics MH - DNA Polymerase II/metabolism MH - *Gene Expression Regulation MH - Gene Silencing MH - HeLa Cells MH - Humans MH - Lamin Type A/*genetics MH - Nuclear Lamina/metabolism PMC - PMC2607069 EDAT- 2009/01/15 09:00 MHDA- 2009/02/04 09:00 PMCR- 2009/06/15 CRDT- 2009/01/15 09:00 PHST- 2009/01/15 09:00 [entrez] PHST- 2009/01/15 09:00 [pubmed] PHST- 2009/02/04 09:00 [medline] PHST- 2009/06/15 00:00 [pmc-release] AID - 22/24/3409 [pii] AID - 10.1101/gad.1735208 [doi] PST - ppublish SO - Genes Dev. 2008 Dec 15;22(24):3409-21. doi: 10.1101/gad.1735208.