RT Journal Article
SR Electronic
T1 An atlas of lamina-associated chromatin across thirteen human cell types reveals cell-type-specific and multiple subtypes of peripheral heterochromatin
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.23.218768
DO 10.1101/2020.07.23.218768
A1 Kathleen C. Keough
A1 Parisha P. Shah
A1 Nadeera M. Wickramasinghe
A1 Carolyn E. Dundes
A1 Angela Chen
A1 Rachel E.A. Salomon
A1 Sean Whalen
A1 Kyle M. Loh
A1 Nicole Dubois
A1 Katherine S. Pollard
A1 Rajan Jain
YR 2020
UL http://biorxiv.org/content/early/2020/07/24/2020.07.23.218768.abstract
AB Three-dimensional genome organization, specifically organization of heterochromatin at the nuclear periphery, coordinates cell type-specific gene regulation. While defining various histone modifications and chromatin-associated proteins in multiple cell types has provided important insights into epigenetic regulation of gene expression and cellular identity, peripheral heterochromatin has not been mapped comprehensively and relatively few examples have emerged detailing the role of peripheral heterochromatin in cellular identity, cell fate choices, and/or organogenesis. In this study, we define nuclear peripheral heterochromatin organization signatures based on association with LAMIN B1 and/or dimethylation of lysine 9 on H3 (H3K9me2) across thirteen human cell types encompassing pluripotent stem cells, intermediate progenitors and differentiated cells from all three germ layers. Genomic analyses across this atlas reveal that lamin-associated chromatin is organized into at least two different compartments, defined by differences in genome coverage, chromatin accessibility, residence of transposable elements, replication timing domains, and gene complements. Our datasets reveal that only a small subset of lamin-associated chromatin domains are cell type invariant, underscoring the complexity of peripheral heterochromatin organization. Moreover, by integrating peripheral chromatin maps with transcriptional data, we find evidence of cooperative shifts between chromatin structure and gene expression associated with each cell type. This atlas of peripheral chromatin provides the largest resource to date for peripheral chromatin organization and a deeper appreciation for how this organization may impact the establishment and maintenance of cellular identity.Competing Interest StatementK.C.K., P.P.S., R.J., C.E.D., R.E.A.S. and K.M.L. have nothing to disclose. A.C. is currently an employee of Orca Bio. K.S.P. is a consultant for Tenaya Therapeutics.AIC:Akaike Information CriterionCE:constitutive early replication domainCL:constitutive late replication domainCM:cardiomyocyteCTI:cell-type-invariantESC:embryonic stem cellKb:kilobases (1000 basepairs)KDD:K9-dimethyl domain, or H3K9me2-associated domainLAD:lamina associated domainLB1:LAMIN-B1LTR:long terminal repeatmESC:mouse embryonic stem cell T1-LAD: Type 1 LADT1-LAD/KDDs:Type 1 LAD overlapping a KDD T2-LAD: Type 2 LADT2-LAD/KDDs:Type 2 LAD overlapping a KDDTE:transposable element