Interaction between the inner nuclear membrane lamin B receptor and the heterochromatic methyl binding protein, MeCP2

• Published in: Experimental cell research Vol. 315; no. 11; pp. 1895 - 1903
• Main Authors: Guarda, Alessia, Bolognese, Fabrizio, Bonapace, Ian Marc, Badaracco, Gianfranco
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-07-2009; Elsevier BV
• Subjects: 60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Base Sequence; CELL MEMBRANES; Cellular biology; DNA; DNA Primers - genetics; Epigenesis, Genetic; Genetic Complementation Test; Genomics; HeLa Cells; HETEROCHROMATIN; Heterochromatin - metabolism; Humans; IN VITRO; IN VIVO; Lamin B Receptor; LBR; Luminescent Proteins - genetics; Luminescent Proteins - metabolism; MeCP2; Membranes; Methyl-CpG-Binding Protein 2 - chemistry; Methyl-CpG-Binding Protein 2 - genetics; Methyl-CpG-Binding Protein 2 - metabolism; METHYLATION; Microscopy, Confocal; Molecular biology; Multiprotein Complexes; Nuclear Envelope - metabolism; Nuclear membrane; Protein Interaction Domains and Motifs; Proteins; RECEPTORS; Receptors, Cytoplasmic and Nuclear - chemistry; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Sequence Deletion; Transfection; Nuclear membrane; MeCP2; Heterochromatin; LBR
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2009.01.019

The nuclear membrane has an important role for the dynamic regulation of the genome, besides the well-established cytoskeletal function. The nuclear lamina is emerging as an important player in the organization of the position and functional state of interphase chromosomes. Epigenetic modifications such as DNA methylation and histone modifications are required for genome reprogramming during development, tissue-specific gene expression and global gene silencing. The Methyl-CpG binding protein MeCP2 binds methyl-CpG dinucleotides in the mammalian genome and functions as a transcriptional repressor
in vivo by interacting with Sin3A, thereby recruiting histone deacetylases (HDAC). MeCP2 also mediates the formation of higher-order chromatin structures contributing to determine the architectural organization of the nucleus. In this paper, we show that MeCP2 interacts
in vitro and
in vivo with the inner nuclear membrane protein LBR and that the unstructured aminoacidic sequence linking the MBD and TRD domains of MeCP2 is responsible for this association. The formation of an LBR–MeCP2 protein complex might help providing a molecular explanation to the distribution of part of the heterochromatin at the nuclear periphery linked to inner membrane.