TY - JOUR T1 - An atlas of lamina-associated chromatin across twelve human cell types reveals an intermediate chromatin subtype JF - bioRxiv DO - 10.1101/2020.07.23.218768 SP - 2020.07.23.218768 AU - Kathleen C. Keough AU - Parisha P. Shah AU - Ketrin Gjoni AU - Garrett T. Santini AU - Nadeera M. Wickramasinghe AU - Carolyn E. Dundes AU - Ashley Karnay AU - Angela Chen AU - Rachel E.A. Salomon AU - Patrick J. Walsh AU - Son C. Nguyen AU - Sean Whalen AU - Eric F. Joyce AU - Kyle M. Loh AU - Nicole Dubois AU - Katherine S. Pollard AU - Rajan Jain Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/11/02/2020.07.23.218768.abstract N2 - Association of chromatin with lamin proteins at the nuclear periphery has emerged as a potential mechanism to coordinate cell type-specific gene expression and maintain cellular identity via gene silencing. Unlike many histone modifications and chromatin-associated proteins, lamin-associated domains (LADs) have yet to be mapped genome-wide in a diverse panel of human cell types, which has limited our understanding of the role peripheral chromatin plays in development and disease. To address this gap, we mapped LAMIN B1 (LB1) across twelve human cell types encompassing pluripotent stem cells, intermediate progenitors, and differentiated cells from all three germ layers. Integrative analyses of this atlas of peripheral chromatin with publicly available genomic data, as well as gene expression and repressive histone maps generated for this study, revealed that in all twelve cellular contexts lamin-associated chromatin is organized into at least two subtypes defined by differences in LB1 occupancy, gene expression, chromatin accessibility, transposable elements, replication timing, and radial positioning. Most genes gain or lose LB1 occupancy consistent with their cell type along developmental trajectories; however, we also identified examples where the enhancer, but not the gene body and promoter, change LAD state. Imaging of fluorescently labeled DNA in single cells validated these transitions and showed intermediate radial positioning of LADs that are gene dense, relatively accessible, and dynamic across development. This atlas represents the largest resource to date for peripheral chromatin organization studies.Competing Interest StatementK.K. is currently an employee of FaunaBio. A.C. is currently an employee of Orca Bio. K.S.P. is a consultant for Tenaya Therapeutics.ChIPchromatin immunoprecipitationESCembryonic stem cellFISHfluorescence in situ hybridizationGOgene ontologyH3K9me2dimethylated histone H3 lysine 9HMMHidden Markov ModelIQRinterquartile rangekbkilobases (1,000 basepairs)KDDK9-dimethyl domain, or H3K9me2-associated domainLADlamina-associated domainLB1LAMIN B1Mbmegabases (1,000,000 basepairs)qRT-PCRquantitative reverse transcription PCRT1-KDDType 1 KDDT1-LADType 1 LADT2-KDDType 2 KDDT2-LADType 2 LADTPMtranscripts per million reads ER -