title: Distinct features of lamin A-interacting chromatin domains mapped by ChIP-sequencing from sonicated or micrococcal nuclease-digested chromatin.
abstract: The nuclear lamina has been shown to interact with the genome through lamina-associated domains (LADs). LADs have been identified by DamID, a proximity labeling assay, and more recently by chromatin immunoprecipitation-sequencing (ChIP-seq) of A- and B-type lamins. LADs form megabase-size domains at the nuclear periphery, they are gene-poor and mostly heterochromatic. Here, we show that the mode of chromatin fragmentation for ChIP, namely bath sonication or digestion with micrococcal nuclease (MNase), leads to the discovery of common but also distinct sets of lamin-interacting domains, or LiDs. Using ChIP-seq, we show the existence of lamin A/C (LMNA) LiDs with distinct gene contents, histone composition enrichment and relationships to lamin B1-interacting domains. The extent of genome coverage of lamin A/C (LMNA) LiDs in sonicated or MNase-digested chromatin is similar (∼730 megabases); however over half of these domains are uniquely detected in sonicated or MNase-digested chromatin. Sonication-specific LMNA LiDs are gene-poor and devoid of a broad panel of histone modifications, while MNase-specific LMNA LiDs are of higher gene density and are enriched in H3K9me3, H3K27me3 and in histone variant H2A.Z. LMNB1 LiDs are gene-poor and show no or little enrichment in these marks. Comparison of published LMNB1 DamID LADs with LMNB1 and LMNA LiDs identified here by ChIP-seq further shows that LMNA can associate with 'open' chromatin domains displaying euchromatin characteristics, and which are not associated with LMNB1. The differential genomic and epigenetic properties of lamin-interacting domains reflect the existence of distinct LiD populations identifiable in different chromatin contexts, including nuclease-accessible regions presumably localized in the nuclear interior.
authors.affiliation: a Department of Molecular Medicine, Institute of Basic Medical Sciences ; University of Oslo, and Norwegian Center for Stem Cell Research , Oslo , Norway.
authors.forename: Eivind G
authors.initials: EG
authors.lastname: Lund
authors.forename: Isabelle
authors.initials: I
authors.lastname: Duband-Goulet
authors.forename: Anja
authors.initials: A
authors.lastname: Oldenburg
authors.forename: Brigitte
authors.initials: B
authors.lastname: Buendia
authors.forename: Philippe
authors.initials: P
authors.lastname: Collas
mesh_terms: D021581:Active Transport, Cell Nucleus; D002843:Chromatin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D022041:Euchromatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D023281:Genomics; D006367:HeLa Cells; D059014:High-Throughput Nucleotide Sequencing; D006657:Histones / Q000378:metabolism; D006801:Humans; D034904:Lamin Type A / Q000378:metabolism*; D008836:Micrococcal Nuclease / Q000378:metabolism*; D034881:Nuclear Lamina / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013010:Sonication
chemical_list: D002843:Chromatin; D022041:Euchromatin; D006657:Histones; D034904:Lamin Type A; D008836:Micrococcal Nuclease
keywords: ChIP; ChIP, chromatin immunoprecipitation; ChIP-seq, ChIP and high-throughput sequencing; DamID, DNA adenine methyltransferase identification; IGV, integrated genomic viewer; LAD, lamina-associated domain; LiD, lamin-interacting domain; MNase, micrococcal nuclease; chromatin; hPTM, histone post-translational modification; lamin-interacting domain; micrococcal nuclease; nuclear lamin; sonication