The nuclear lamina binds chromatin in vitro and is thought to function in its organization, but genes that interact with it are unknown. Using an in vivo approach, we identified ∼500 Drosophila melanogaster genes that interact with B-type lamin (Lam). These genes are transcriptionally silent and late replicating, lack active histone marks and are widely spaced. These factors collectively predict lamin binding behavior, indicating that the nuclear lamina integrates variant and invariant chromatin features. Consistently, proximity of genomic regions to the nuclear lamina is partly conserved between cell types, and induction of gene expression or active histone marks reduces Lam binding. Lam target genes cluster in the genome, and these clusters are coordinately expressed during development. This genome-wide analysis gives clear insight into the nature and dynamic behavior of the genome at the nuclear lamina, and implies that intergenic DNA functions in the global organization of chromatin in the nucleus.
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We thank J. Delrow and M. Aronszajn (Genomics facility, Fred Hutchinson Cancer Research Center) for providing and annotating of cDNA arrays; N. Stuurman for plasmids, antibodies and helpful suggestions; F. Greil and C. Moorman for valuable technical advice; G. Hart for advice on statistical methods; M. Heimerikx and the NKI microarray facility for technical support; L. Guelen, H. van der Velde, J. Hendriksen and D. Engelsma for scoring of the FISH images; and J.M. Boer, S. Nijman, F. van Leeuwen, J. Neefjes, M. van Lohuizen and members of the van Steensel and Fornerod labs for helpful discussions and critical reading of the manuscript. This work was supported by a Marie Curie European Community Training and Mobility grant to H.P. and an European Young Investigator Award to B.v.S.
Estimate of DNA content in the nuclear periphery. (PDF 273 kb)
Genomic Lamin binding in embryonic cells shows significant correspondence to polytene chromosome nuclear envelope contacts in larvae. (PDF 116 kb)
Genes bound by Lam are repressed, lack active histone marks and are late replicating. (PDF 157 kb)
The binding pattern of Lam is distinct from that of HP1 and Su(var)3-9. (PDF 1100 kb)
Developmental expression profiles of Lam target gene clusters. (PDF 99 kb)
Excel spreadsheet containing DamID data, clustering data, expression profiling, flanking intergenic region lengths, probe annotation and gene ontology analysis of Lam-binding genes. (XLS 6469 kb)
Characteristics of FISH probes. (PDF 86 kb)
Multiple regression analysis of Lam binding. (PDF 64 kb)
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Lamin A/C and Emerin depletion impacts chromatin organization and dynamics in the interphase nucleus
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