De novo reconstruction of satellite repeat units from sequence data [METHODS]
Satellite DNA are long tandemly repeating sequences in a genome and may be organized as high-order repeats (HORs). They are enriched in centromeres and are challenging to assemble. Existing algorithms for identifying satellite repeats either require the complete assembly of satellites or only work for simple repeat structures without HORs. Here we describe Satellite Repeat Finder (SRF), a new algorithm for reconstructing satellite repeat units and HORs from accurate reads or assemblies without prior knowledge on repeat structures. Applying SRF to real sequence data, we show that SRF could reconstruct known satellites in hu...
Source: Genome Research - December 1, 2023 Category: Genetics & Stem Cells Authors: Zhang, Y., Chu, J., Cheng, H., Li, H. Tags: METHODS Source Type: research
Proteome-wide structural analysis quantifies structural conservation across distant species [RESEARCH]
Traditional evolutionary biology research mainly relies on sequence information to infer evolutionary relationships between genes or proteins. In contrast, protein structural information has long been overlooked, although structures are more conserved and closely linked to the functions than the sequences. To address this gap, we conducted a proteome-wide structural analysis using experimental and computed protein structures for organisms from the three distinct domains, including Homo sapiens (eukarya), Escherichia coli (bacteria), and Methanocaldococcus jannaschii (archaea). We reveal the distribution of structural simil...
Source: Genome Research - December 1, 2023 Category: Genetics & Stem Cells Authors: Zhang, S., Zhang, T., Fu, Y. Tags: RESEARCH Source Type: research
Genome-wide chromatin interaction profiling reveals a vital role of super-enhancers and rearrangements in host enhancer contacts during BmNPV infection [RESEARCH]
As influential regulatory elements in the genome, enhancers control gene expression under specific cellular conditions, and such connections are dynamic under different conditions. However, because of the lack of a genome-wide enhancer–gene connection map, the roles and regulatory pattern of enhancers were poorly investigated in insects, and the dynamic changes of enhancer contacts and functions under different conditions remain elusive. Here, combining Hi-C, ATAC-seq, and H3K27ac ChIP-seq data, we generate the genome-wide enhancer–gene map of silkworm and identify super-enhancers with a role in regulating the ...
Source: Genome Research - December 1, 2023 Category: Genetics & Stem Cells Authors: Zhao, S., Li, Y., Chen, G., Wang, X., Chen, N., Wu, X. Tags: RESEARCH Source Type: research
Telomeric repeat evolution in the phylum Nematoda revealed by high-quality genome assemblies and subtelomere structures [RESEARCH]
Telomeres are composed of tandem arrays of telomeric-repeat motifs (TRMs) and telomere-binding proteins (TBPs), which are responsible for ensuring end-protection and end-replication of chromosomes. TRMs are highly conserved owing to the sequence specificity of TBPs, although significant alterations in TRM have been observed in several taxa, except Nematoda. We used public whole-genome sequencing data sets to analyze putative TRMs of 100 nematode species and determined that three distinct branches included specific novel TRMs, suggesting that evolutionary alterations in TRMs occurred in Nematoda. We focused on one of the th...
Source: Genome Research - December 1, 2023 Category: Genetics & Stem Cells Authors: Lim, J., Kim, W., Kim, J., Lee, J. Tags: RESEARCH Source Type: research
miRNA-like secondary structures in maize (Zea mays) genes and transposable elements correlate with small RNAs, methylation, and expression [RESEARCH]
In this study, we used two bioinformatic methods to predict local secondary structures across features of the maize genome, focusing on small regions that had similar folding properties to pre-miRNA loci. We found miRNA-like secondary structures to be common in genes and most, but not all, superfamilies of RNA and DNA transposable elements (TEs). The miRNA-like regions map to a higher diversity of smRNAs than regions without miRNA-like structure, explaining up to 27% of variation in smRNA mapping for some TE superfamilies. This mapping bias is more pronounced among putatively autonomous TEs relative to nonautonomous TEs. G...
Source: Genome Research - December 1, 2023 Category: Genetics & Stem Cells Authors: Martin, G. T., Solares, E., Guadardo-Mendez, J., Muyle, A., Bousios, A., Gaut, B. S. Tags: RESEARCH Source Type: research
Transposon wave remodeled the epigenomic landscape in the rapid evolution of X-Chromosome dosage compensation [RESEARCH]
Sex chromosome dosage compensation is a model to understand the coordinated evolution of transcription; however, the advanced age of the sex chromosomes in model systems makes it difficult to study how the complex regulatory mechanisms underlying chromosome-wide dosage compensation can evolve. The sex chromosomes of Poecilia picta have undergone recent and rapid divergence, resulting in widespread gene loss on the male Y, coupled with complete X Chromosome dosage compensation, the first case reported in a fish. The recent de novo origin of dosage compensation presents a unique opportunity to understand the genetic and evol...
Source: Genome Research - December 1, 2023 Category: Genetics & Stem Cells Authors: Metzger, D. C. H., Porter, I., Mobley, B., Sandkam, B. A., Fong, L. J. M., Anderson, A. P., Mank, J. E. Tags: RESEARCH Source Type: research
Cellular age explains variation in age-related cell-to-cell transcriptome variability [RESEARCH]
Organs and tissues age at different rates within a single individual. Such asynchrony in aging has been widely observed at multiple levels, from functional hallmarks, such as anatomical structures and physiological processes, to molecular endophenotypes, such as the transcriptome and metabolome. However, we lack a conceptual framework to understand why some components age faster than others. Just as demographic models explain why aging evolves, here we test the hypothesis that demographic differences among cell types, determined by cell-specific differences in turnover rate, can explain why the transcriptome shows signs of...
Source: Genome Research - December 1, 2023 Category: Genetics & Stem Cells Authors: Yang, M., Harrison, B. R., Promislow, D. E. L. Tags: RESEARCH Source Type: research
E4F1 and ZNF148 are transcriptional activators of the -57A > C and wild-type TERT promoter [RESEARCH]
Point mutations within the TERT promoter are the most recurrent somatic noncoding mutations identified across different cancer types, including glioblastoma, melanoma, hepatocellular carcinoma, and bladder cancer. They are most abundant at –146C > T and –124C > T, and rarer at –57A > C, with the latter originally described as a familial case, but subsequently shown also to occur somatically. All three mutations create de novo E26-specific (ETS) binding sites and result in activation of the TERT gene, allowing cancer cells to achieve replicative immortality. Here, we used a systematic proteomics s...
Source: Genome Research - December 1, 2023 Category: Genetics & Stem Cells Authors: Chua, B. H., Zaal Anuar, N., Ferry, L., Domrane, C., Wittek, A., Mukundan, V. T., Jha, S., Butter, F., Tenen, D. G., Defossez, P.-A., Kappei, D. Tags: RESEARCH Source Type: research
Characterization of human transcription factor function and patterns of gene regulation in HepG2 cells [RESEARCH]
Transcription factors (TFs) are trans-acting proteins that bind cis-regulatory elements (CREs) in DNA to control gene expression. Here, we analyzed the genomic localization profiles of 529 sequence-specific TFs and 151 cofactors and chromatin regulators in the human cancer cell line HepG2, for a total of 680 broadly termed DNA-associated proteins (DAPs). We used this deep collection to model each TF's impact on gene expression, and identified a cohort of 26 candidate transcriptional repressors. We examine high occupancy target (HOT) sites in the context of three-dimensional genome organization and show biased motif placeme...
Source: Genome Research - December 1, 2023 Category: Genetics & Stem Cells Authors: Moyers, B. A., Partridge, E. C., Mackiewicz, M., Betti, M. J., Darji, R., Meadows, S. K., Newberry, K. M., Brandsmeier, L. A., Wold, B. J., Mendenhall, E. M., Myers, R. M. Tags: RESEARCH Source Type: research
The human genome contains over a million autonomous exons [RESEARCH]
Mammalian mRNA and lncRNA exons are often small compared to introns. The exon definition model predicts that exons splice autonomously, dependent on proximal exon sequence features, explaining their delineation within large introns. This model has not been examined on a genome-wide scale, however, leaving open the question of how often mRNA and lncRNA exons are autonomous. It is also unknown how frequently such exons can arise by chance. Here, we directly assayed large fragments (500–1000 bp) of the human genome by exon trapping, which detects exons spliced into a heterologous transgene, here designed with a large in...
Source: Genome Research - December 1, 2023 Category: Genetics & Stem Cells Authors: Stepankiw, N., Yang, A. W. H., Hughes, T. R. Tags: RESEARCH Source Type: research
Aberrant landscapes of maternal meiotic crossovers contribute to aneuploidies in human embryos [METHOD]
Meiotic recombination is crucial for human genetic diversity and chromosome segregation accuracy. Understanding its variation across individuals and the processes by which it goes awry are long-standing goals in human genetics. Current approaches for inferring recombination landscapes either rely on population genetic patterns of linkage disequilibrium (LD)—capturing a time-averaged view or direct detection of crossovers in gametes or multi-generation pedigrees, which limits dataset scale and availability. Here, we introduce an approach for inferring sex-specific recombination landscapes using data from preimplantati...
Source: Genome Research - December 1, 2023 Category: Genetics & Stem Cells Authors: Ariad, D., Madjunkova, S., Madjunkov, M., Chen, S., Abramov, R., Librach, C., McCoy, R. C. Tags: METHOD Source Type: research
Integrating SNVs and CNAs on a phylogenetic tree from single-cell DNA sequencing data [METHOD]
Single-cell DNA sequencing enables the construction of evolutionary trees that can reveal how tumors gain mutations and grow. Different whole-genome amplification procedures render genomic materials of different characteristics, often suitable for the detection of either single-nucleotide variation or copy number aberration, but not ideally for both. Consequently, this hinders the inference of a comprehensive phylogenetic tree and limits opportunities to investigate the interplay of SNVs and CNAs. Existing methods such as SCARLET and COMPASS require that the SNVs and CNAs are detected from the same sets of cells, which is ...
Source: Genome Research - November 22, 2023 Category: Genetics & Stem Cells Authors: Zhang, L., Bass, H. W., Irianto, J., Mallory, X. Tags: METHOD Source Type: research
Proteome-wide structural analysis quantifies structural conservation across distant species [RESEARCH]
Traditional evolutionary biology research mainly relies on sequence information to infer evolutionary relationships between genes or proteins. In contrast, protein structural information has long been overlooked, although structures are more conserved and closely linked to the functions than the sequences. To address this gap, we conducted a proteome-wide structural analysis using experimental and computed protein structures for organisms from the three distinct domains, including Homo sapiens (eukarya), Escherichia coli (bacteria), and Methanocaldococcus jannaschii (archaea). We reveal the distribution of structural simil...
Source: Genome Research - November 22, 2023 Category: Genetics & Stem Cells Authors: Zhang, S., Zhang, T., Fu, Y. Tags: RESEARCH Source Type: research
E4F1 and ZNF148 are transcriptional activators of the -57A > C and wild-type TERT promoter [RESEARCH]
Point mutations within the TERT promoter are the most recurrent somatic noncoding mutations identified across different cancer types, including glioblastoma, melanoma, hepatocellular carcinoma, and bladder cancer. They are most abundant at –146C > T and –124C > T, and rarer at –57A > C, with the latter originally described as a familial case, but subsequently shown also to occur somatically. All three mutations create de novo E26-specific (ETS) binding sites and result in activation of the TERT gene, allowing cancer cells to achieve replicative immortality. Here, we used a systematic proteomics s...
Source: Genome Research - November 21, 2023 Category: Genetics & Stem Cells Authors: Chua, B. H., Zaal Anuar, N., Ferry, L., Domrane, C., Wittek, A., Mukundan, V. T., Jha, S., Butter, F., Tenen, D. G., Defossez, P.-A., Kappei, D. Tags: RESEARCH Source Type: research
De novo reconstruction of satellite repeat units from sequence data [METHOD]
Satellite DNA are long tandemly repeating sequences in a genome and may be organized as high-order repeats (HORs). They are enriched in centromeres and are challenging to assemble. Existing algorithms for identifying satellite repeats either require the complete assembly of satellites or only work for simple repeat structures without HORs. Here we describe Satellite Repeat Finder (SRF), a new algorithm for reconstructing satellite repeat units and HORs from accurate reads or assemblies without prior knowledge on repeat structures. Applying SRF to real sequence data, we show that SRF could reconstruct known satellites in hu...
Source: Genome Research - November 21, 2023 Category: Genetics & Stem Cells Authors: Zhang, Y., Chu, J., Cheng, H., Li, H. Tags: METHOD Source Type: research
