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Pre‐Lamin A processing is linked to heterochromatin organization
Author(s) -
Lattanzi Giovanna,
Columbaro Marta,
Mattioli Elisabetta,
Cenni Vittoria,
Camozzi Daria,
Wehnert Manfred,
Santi Spartaco,
Riccio Massimo,
Del Coco Rosalba,
Maraldi Nadir M.,
Squarzoni Stefano,
Foisner Roland,
Capanni Cristina
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21467
Subject(s) - lamin , heterochromatin , chromatin , histone , heterochromatin protein 1 , biology , prenylation , microbiology and biotechnology , nuclear lamina , acetylation , cleavage (geology) , progeria , cell nucleus , euchromatin , nuclear protein , genetics , nucleus , biochemistry , dna , gene , transcription factor , enzyme , paleontology , fracture (geology)
Pre‐lamin A undergoes subsequent steps of post‐translational modification at its C‐terminus, including farnesylation, methylation, and cleavage by ZMPSTE24 metalloprotease. Here, we show that accumulation of different intermediates of pre‐lamin A processing in nuclei, induced by expression of mutated pre‐lamin A, differentially affected chromatin organization in human fibroblasts. Unprocessed (non‐farnesylated) pre‐lamin A accumulated in intranuclear foci, caused the redistribution of LAP2alpha and of the heterochromatin markers HP1alpha and trimethyl‐K9‐histone 3, and triggered heterochromatin localization in the nuclear interior. In contrast, the farnesylated and carboxymethylated lamin A precursor accumulated at the nuclear periphery and caused loss of heterochromatin markers and Lap2alpha in enlarged nuclei. Interestingly, pre‐lamin A bound both HP1alpha and LAP2alpha in vivo, but the farnesylated form showed reduced affinity for HP1alpha. Our data show a link between pre‐lamin A processing and heterochromatin remodeling and have major implications for understanding molecular mechanisms of human diseases linked to mutations in lamins. J. Cell. Biochem. 102: 1149–1159, 2007. © 2007 Wiley‐Liss, Inc.