Epigenetic patterns in a complete human genome

作者：Ariel Gershman, Michael E.G. Sauria, Xavi Guitart, Mitchell R. Vollger, Paul W. Hook, Savannah J. Hoyt, Miten Jain, Alaina Shumate, Roham Razaghi, Sergey Koren, Nicolas Altemose, Gina V. Caldas, Glennis A. Logsdon, Arang Rhie, Evan E. Eichler, Michael C. Schatz, Rachel J. O’Neill, Adam M. Phillippy, Karen H. Miga, Winston Timp · 发表于：Science · 年份：2022 · DOI：10.1126/science.abj5089 · 被引用次数：332 · 研究领域：Epigenetics and DNA Methylation、Genomic variations and chromosomal abnormalities、Genomics and Chromatin Dynamics

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.