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A complete understanding of gene regulation will require the mapping of these chromatin features in small cell number samples. Here we describe a novel genome-wide chromatin profiling technology, named as Nicking Enzyme Epitope targeted DNA sequencing (NEED-seq). NEED-seq offers antibody-targeted controlled nicking by Nt.CviPII-pGL fusion to study specific protein\u2013DNA complexes in formaldehyde fixed cells, allowing for both visual and genomic resolution of epitope bound chromatin. When applied to nuclei, NEED-seq yielded genome-wide profile of chromatin-associated proteins and histone PTMs. Additionally, NEED-seq of lamin B1 and B2 demonstrated their association with heterochromatin. Lamin B1- and B2-associated domains (LAD) segregated to three different states, and states with stronger LAD correlated with heterochromatic marks. Hi-C analysis displayed A and B compartment with equal lamin B1 and B2 distribution, although methylated DNA remained high in B compartment. LAD clustering with Hi-C resulted in subcompartments, with lamin B1 and B2 partitioning to facultative and constitutive heterochromatin, respectively, and were associated with neuronal development. Thus, lamin B1 and B2 show structural and functional partitioning in mammalian nucleus.<\/jats:p>","DOI":"10.1093\/nar\/gkae1317","type":"journal-article","created":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T15:27:39Z","timestamp":1735226859000},"source":"Crossref","is-referenced-by-count":5,"title":["Distinct structural and functional heterochromatin partitioning of lamin B1 and lamin B2 revealed using genome-wide nicking enzyme epitope targeted DNA sequencing"],"prefix":"10.1093","volume":"53","author":[{"given":"Sagnik","family":"Sen","sequence":"first","affiliation":[{"name":"Molecular Genetics and Genomics, New England Biolabs, Inc , 240 County Road , Ipswich , MA\u00a0 01938 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre-Olivier","family":"Est\u00e8ve","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Genomics, New England Biolabs, Inc , 240 County Road , Ipswich , MA\u00a0 01938 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthikeyan","family":"Raman","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Genomics, New England Biolabs, Inc , 240 County Road , Ipswich , MA\u00a0 01938 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Beaulieu","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Genomics, New England Biolabs, Inc , 240 County Road , Ipswich , MA\u00a0 01938 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang\u00a0Gyeong","family":"Chin","sequence":"additional","affiliation":[{"name":"PMBBRC, Gyeongsang National University , Jinju\u00a0 52828 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George\u00a0R","family":"Feehery","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Genomics, New England Biolabs, Inc , 240 County Road , Ipswich , MA\u00a0 01938 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udayakumar\u00a0S","family":"Vishnu","sequence":"additional","affiliation":[{"name":"Genome Technologies, Epicypher Inc , Durham , NC\u00a0 27709 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang-yong","family":"Xu","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Genomics, New England Biolabs, Inc , 240 County Road , Ipswich , MA\u00a0 01938 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James\u00a0C","family":"Samuelson","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Genomics, New England Biolabs, Inc , 240 County Road , Ipswich , MA\u00a0 01938 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1710-0588","authenticated-orcid":false,"given":"Sriharsa","family":"Pradhan","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Genomics, New England Biolabs, Inc , 240 County Road , Ipswich , MA\u00a0 01938 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,1,16]]},"reference":[{"key":"2025020306180338900_B1","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/nrm2640","article-title":"Epigenetic inheritance during the cell cycle","volume":"10","author":"Probst","year":"2009","journal-title":"Nat. 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