Dataset Information

Complete genomic and epigenetic maps of human centromeres.

ABSTRACT: Existing human genome assemblies have almost entirely excluded repetitive sequences within and near centromeres, limiting our understanding of their organization, evolution, and functions, which include facilitating proper chromosome segregation. Now, a complete, telomere-to-telomere human genome assembly (T2T-CHM13) has enabled us to comprehensively characterize pericentromeric and centromeric repeats, which constitute 6.2% of the genome (189.9 megabases). Detailed maps of these regions revealed multimegabase structural rearrangements, including in active centromeric repeat arrays. Analysis of centromere-associated sequences uncovered a strong relationship between the position of the centromere and the evolution of the surrounding DNA through layered repeat expansions. Furthermore, comparisons of chromosome X centromeres across a diverse panel of individuals illuminated high degrees of structural, epigenetic, and sequence variation in these complex and rapidly evolving regions.

SUBMITTER: Altemose N

PROVIDER: S-EPMC9233505 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Complete genomic and epigenetic maps of human centromeres.

Altemose Nicolas N Logsdon Glennis A GA Bzikadze Andrey V AV Sidhwani Pragya P Langley Sasha A SA Caldas Gina V GV Hoyt Savannah J SJ Uralsky Lev L Ryabov Fedor D FD Shew Colin J CJ Sauria Michael E G MEG Borchers Matthew M Gershman Ariel A Mikheenko Alla A Shepelev Valery A VA Dvorkina Tatiana T Kunyavskaya Olga O Vollger Mitchell R MR Rhie Arang A McCartney Ann M AM Asri Mobin M Lorig-Roach Ryan R Shafin Kishwar K Lucas Julian K JK Aganezov Sergey S Olson Daniel D de Lima Leonardo Gomes LG Potapova Tamara T Hartley Gabrielle A GA Haukness Marina M Kerpedjiev Peter P Gusev Fedor F Tigyi Kristof K Brooks Shelise S Young Alice A Nurk Sergey S Koren Sergey S Salama Sofie R SR Paten Benedict B Rogaev Evgeny I EI Streets Aaron A Karpen Gary H GH Dernburg Abby F AF Sullivan Beth A BA Straight Aaron F AF Wheeler Travis J TJ Gerton Jennifer L JL Eichler Evan E EE Phillippy Adam M AM Timp Winston W Dennis Megan Y MY O'Neill Rachel J RJ Zook Justin M JM Schatz Michael C MC Pevzner Pavel A PA Diekhans Mark M Langley Charles H CH Alexandrov Ivan A IA Miga Karen H KH

Science (New York, N.Y.) 20220401 6588

Existing human genome assemblies have almost entirely excluded repetitive sequences within and near centromeres, limiting our understanding of their organization, evolution, and functions, which include facilitating proper chromosome segregation. Now, a complete, telomere-to-telomere human genome assembly (T2T-CHM13) has enabled us to comprehensively characterize pericentromeric and centromeric repeats, which constitute 6.2% of the genome (189.9 megabases). Detailed maps of these regions reveale ...[more]

PMID: 35357911

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Project description:Deletion of native centromeres in the human fungal pathogen Cryptococcus deuterogattii leads to neocentromere formation. Native centromeres span truncated transposable elements, while neocentromeres do not and instead span actively expressed genes. To explore the epigenetic organization of neocentromeres, we analyzed the distribution of the heterochromatic histone modification H3K9me2, 5mC DNA methylation and the euchromatin mark H3K4me2. Native centromeres are enriched for both H3K9me2 and 5mC DNA methylation marks and are devoid of H3K4me2, while neocentromeres do not exhibit any of these features. Neocentromeres in cen10Δ mutants are unstable and chromosome-chromosome fusions occur. After chromosome fusion, the neocentromere is inactivated and the native centromere of the chromosome fusion partner remains as the sole, active centromere. In the present study, the active centromere of a fused chromosome was deleted to investigate if epigenetic memory promoted the re-activation of the inactive neocentromere. Our results show that the inactive neocentromere is not re-activated and instead a novel neocentromere forms directly adjacent to the deleted centromere of the fused chromosome. To study the impact of transcription on centromere stability, the actively expressed URA5 gene was introduced into the CENP-A bound regions of a native centromere. The introduction of the URA5 gene led to a loss of CENP-A from the native centromere, and a neocentromere formed adjacent to the native centromere location. Remarkably, the inactive, native centromere remained enriched for heterochromatin, yet the integrated gene was expressed and devoid of H3K9me2. A cumulative analysis of multiple CENP-A distribution profiles revealed centromere drift in C. deuterogattii, a previously unreported phenomenon in fungi. The CENP-A-binding shifted within the ORF-free regions and showed a possible association with a truncated transposable element. Taken together, our findings reveal that neocentromeres in C. deuterogattii are highly unstable and are not marked with an epigenetic memory, distinguishing them from native centromeres.

Dataset Information

Complete genomic and epigenetic maps of human centromeres.

Publications

Complete genomic and epigenetic maps of human centromeres.

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