Project description:Centromere identity is defined and maintained epigenetically by the presence of the histone variant CENP-A. How centromeric CENP-A position is specified and precisely maintained through DNA replication is not fully understood. The recently released Telomere-to-Telomere (T2T-CHM13) genome assembly containing the first complete human centromere sequences provides a new resource for examining CENP-A position. Mapping CENP-A position in clones of the same cell line to T2T-CHM13 identified highly similar CENP-A position following multiple cell divisions. In contrast, centromeric CENP-A epialleles were evident at several centromeres of different human cell lines, demonstrating the location of CENP-A enrichment and site of kinetochore recruitment varies among human cells. Across the cell cycle, CENP-A molecules deposited in G1 phase are maintained at their precise position through DNA replication. Thus, despite CENP-A dilution during DNA replication, CENP-A is precisely reloaded onto the same sequences within the daughter centromeres, maintaining unique centromere identity among human cells.
Project description:<p><strong>BACKGROUND:</strong> Traditional Chinese medicine has used <em>Peucedanum praeruptorum</em> Dunn (Apiaceae) for a long time. Various coumarins, including the significant root constituents Praeruptorin (A-E), are the active constituents of the dried roots of P. praeruptorum. Previous transcriptomic and metabolomic studies attempted to elucidate the distribution and biosynthetic network of these medicinal-valuable compounds. However, the lack of a high-quality reference genome impedes an in-depth understanding of genetic traits and, thus, the development of better breeding strategies.</p><p><strong>RESULTS:</strong> The authors assembled a telomere-to-telomere genome by combining PacBio HiFi, ONT ultra- long and Hi-C data. The final genome assembly was approximately 1.798 Gb, assigned to 11 chromosomes and genome completeness >98%. Comparative genomic analysis suggested that <em>P. praeruptorum</em> experienced two WGD events like the ones in the Apiaceae family. By the transcriptomic and metabolomic analysis of the coumarin metabolic pathway, we presented coumarins' spatial and temporal distribution and the expression patterns of critical genes for its biosynthesis. Notably, the <em>COSY</em> and cytochrome <em>P450</em> genes showed tandem duplications on several chromosomes, which may be responsible for the high accumulation of coumarins.</p><p><strong>CONCLUSIONS:</strong> The authors obtained a T2T genome for <em>P. praeruptorum</em>, which provides molecular insights into the chromosomal distribution of the coumarin biosynthetic genes. This high-quality genome is an essential resource for designing engineering strategies for improving the production of these valuable compounds.</p>
Project description:We examined differential expression of genes within 10MBs of telomeres in myoblasts with long or short telomeres We offer telomere looping with telomere length as a partial mechanistic explanation for the changes gene expression that is observed. Compare expression of genes within 10MB of the telomere in normal myoblasts with long (15 kb) and short (6 kb) telomeres.
Project description:We used microarrays to analyze the prevalence of signalling induced by acute telomere dysfunction (as induced by TRF2DBDM expression = Dataset 1) and in TERC- compared to TERC+ HCC (Dataset 2). Keywords: acute telomere dysfunction, hepatocellular cancer
Project description:We performed ATAC-seq on publicly available leukemia cell-lines and used them to predict non-coding regulatory mutations in open-chromatin regions of the genome.
Project description:Gene expression of human knockouts of telomere-protein Rap1 were compared to their wildtype counterparts in mutliple cell lines (available from the ATCC repository). We discovered that Rap1, desite being mostly associated with the telomere, performed a conserved role in transcriptional regulation, as evidenced by a number of genes that were differentially regulated upon deletion of Rap1.