Epigenetic patterns in a complete human genome

The completion of a telomere-to-telomere human reference genome, T2T-CHM13, has resolved complex regions of the genome, including repetitive and homologous regions. Here, we present a high-resolution epigenetic study of previously unresolved sequences, representing entire acrocentric chromosome shor...

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Published inScience (American Association for the Advancement of Science) Vol. 376; no. 6588; p. eabj5089
Main Authors Gershman, Ariel, Sauria, Michael E. G., Guitart, Xavi, Vollger, Mitchell R., Hook, Paul W., Hoyt, Savannah J., Jain, Miten, Shumate, Alaina, Razaghi, Roham, Koren, Sergey, Altemose, Nicolas, Caldas, Gina V., Logsdon, Glennis A., Rhie, Arang, Eichler, Evan E., Schatz, Michael C., O’Neill, Rachel J., Phillippy, Adam M., Miga, Karen H., Timp, Winston
Format Journal Article
LanguageEnglish
Published United States The American Association for the Advancement of Science 01.04.2022
Subjects
Annotations
Assembly
Biomarkers
Cell division
Centromere - genetics
Centromere - metabolism
Centromeres
Chromatin
Chromosomes
CpG Islands
Deoxyribonucleic acid
Disease - genetics
DNA
DNA Methylation
Dynamic stability
Epigenesis, Genetic
Epigenetics
Exploration
Functional Behavioral Assessment
Gene duplication
Gene expression
Gene families
Gene mapping
Genetic Loci
Genome, Human
Genomes
Genomics
Genomics - standards
Histones
Homology
Humans
Kinetochores
Localization
Methylation
Nucleotide sequence
Pattern formation
Protein interaction
Proteins
Reference Standards
Reproduction (copying)
Sequence Analysis, DNA
Structure-function relationships
Telomeres
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Summary:The completion of a telomere-to-telomere human reference genome, T2T-CHM13, has resolved complex regions of the genome, including repetitive and homologous regions. Here, we present a high-resolution epigenetic study of previously unresolved sequences, representing entire acrocentric chromosome short arms, gene family expansions, and a diverse collection of repeat classes. This resource precisely maps CpG methylation (32.28 million CpGs), DNA accessibility, and short-read datasets (166,058 previously unresolved chromatin immunoprecipitation sequencing peaks) to provide evidence of activity across previously unidentified or corrected genes and reveals clinically relevant paralog-specific regulation. Probing CpG methylation across human centromeres from six diverse individuals generated an estimate of variability in kinetochore localization. This analysis provides a framework with which to investigate the most elusive regions of the human genome, granting insights into epigenetic regulation.
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Author Contributions: Conceived the study: K.H.M and W.T.; Coordinated the collaboration: W.T., A.M.P., K.H.M., and A.G.; repeat characterization and satellite DNA assembly: K.H.M. and N.A.; ENCODE and mappability analyses: A.G., M.E.G.S., and M.C.S; CUT&RUN: G.V.C. and N.A.; ONT mapping and methylation calling: N.A., A.R. and S.K.; TE and non-centromeric repeat annotations: S.J.H and R.J.O.; Gene annotation liftover: A.G. and A.S.; SegDup annotations: M.R.V., G.A.L. and E.E.E; marker-assisted mapping of CUT&RUN data: A.R.; HG002 cell culture, nanoNOMe sequencing and analysis: A.G., P.W.H, and R.R.; phylogenetic and aging analysis of NBPF genes: A.G., M.R.V., X.G. and E.E.E.; megalodon methylation calling: M.J.; developed figures: A.G., W.T. and K.H.M; drafted the manuscript: A.G. and W.T.; provided critical feedback and read and approved the final manuscript: all authors.
ISSN:0036-8075
1095-9203
1095-9203
DOI:10.1126/science.abj5089