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Whereas sonication-specific LMNA Li Ds are gene-poor and devoid of a broad panel of histone modifications, MNase-specific LMNA Li Ds are of higher gene density and are enriched in H3K9me3, H3K27me3 and in histone variant H2A. Analysis of published LMNB1 LADs and of LMNB1 Li Ds identified by Ch IP-seq further shows that LMNA can associate with 'open' chromatin domains displaying euchromatin features which are not associated with LMNB1.

The differential genetic and epigenetic properties of lamin-interacting chromatin domains indicate the existence of distinct Li D populations identifiable in different chromatin contexts, including nuclease-accessible 'open' regions presumably localized in the nuclear interior.

LADs localize mainly to the nuclear periphery, they are gene-poor and largely heterochromatic.

Here, we show that the mode of chromatin fragmentation for Ch IP, namely either bath sonication (used to date for Ch IP of nuclear lamins) or digestion with micrococcal nuclease (MNase) leads to the discovery of distinct sets of lamin-interacting domains (which we refer to as Li Ds) with distinct gene content, histone composition enrichment and relationship to lamin B1-interacting domains.

The nuclear lamina interacts with the genome through megabase-size lamina-associated domains (LADs).

LADs have been identified in proximity labeling assays and recently by chromatin immunoprecipitation-sequencing (Ch IP-seq) of A- and B-type lamins.

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We find that total genome coverage by lamin A/C ('LMNA') Li Ds identified in sonicated or MNase-digested chromatin is similar (~730 megabases).

Over half of these domains, however, are uniquely detected in sonicated or MNase-digested chromatin.

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