Using long-read CAGE sequencing to profile cryptic-promoter-derived transcripts and their contribution to the immunopeptidome [METHODS]
Recent studies have shown that the noncoding genome can produce unannotated proteins as antigens that induce immune response. One major source of this activity is the aberrant epigenetic reactivation of transposable elements (TEs). In tumors, TEs often provide cryptic or alternate promoters, which can generate transcripts that encode tumor-specific unannotated proteins. Thus, TE-derived transcripts (TE transcripts) have the potential to produce tumor-specific, but recurrent, antigens shared among many tumors. Identification of TE-derived tumor antigens holds the promise to improve cancer immunotherapy approaches; however, ...
Source: Genome Research - December 27, 2023 Category: Genetics & Stem Cells Authors: Maeng, J. H., Jang, H. J., Du, A. Y., Tzeng, S.-C., Wang, T. Tags: METHODS Source Type: research
Evidence for selfing in a vertebrate from whole-genome sequencing [RESEARCH]
A growing number of recent genomic studies report asexual parthenogenetic reproduction in a wide range of taxa, including vertebrate species from the reptile, bird, and fish lineages. Yet, self-fertilization (selfing) has been recorded only in a single vertebrate, the mangrove killifish Kryptolebias marmoratus. In cichlid fishes, sex determination is notably diverse and can be influenced by the environment, and sequential hermaphroditism has been reported for some species. Here, we present evidence for a case of facultative selfing in the cichlid fish Benitochromis nigrodorsalis, which is otherwise known as biparentally re...
Source: Genome Research - December 27, 2023 Category: Genetics & Stem Cells Authors: Böhne, A., Oguzhan, Z., Chrysostomakis, I., Vitt, S., Meuthen, D., Martin, S., Kukowka, S., Thünken, T. Tags: RESEARCH Source Type: research
tRNA-derived small RNAs are embedded in the gene regulatory network instructing Drosophila metamorphosis [RESEARCH]
We describe experiments to characterize the mode of tsRNA action and, through the use of such gained knowledge, conduct a genome-wide analysis to assess the functions of dynamically expressed tsRNAs. Our results show that the predicted target genes are highly enriched in biological processes specific to this stage of development including metamorphosis. We further show that tsRNA action is required for successful pupation, providing direct support to the hypothesis that tsRNAs accumulated during this stage are critical to the gene expression program at this stage of development. (Source: Genome Research)
Source: Genome Research - December 27, 2023 Category: Genetics & Stem Cells Authors: Shi, J., Xu, J., Ma, J., He, F. Tags: RESEARCH Source Type: research
Spatiotemporal kinetics of CAF-1-dependent chromatin maturation ensures transcription fidelity during S-phase [RESEARCH]
Proper maintenance of epigenetic information after replication is dependent on the rapid assembly and maturation of chromatin. Chromatin Assembly Complex 1 (CAF-1) is a conserved histone chaperone that deposits (H3-H4)2 tetramers as part of the replication-dependent chromatin assembly process. Loss of CAF-1 leads to a delay in chromatin maturation, albeit with minimal impact on steady-state chromatin structure. However, the mechanisms by which CAF-1 mediates the deposition of (H3-H4)2 tetramers and the phenotypic consequences of CAF-1-associated assembly defects are not well understood. We used nascent chromatin occupancy ...
Source: Genome Research - December 27, 2023 Category: Genetics & Stem Cells Authors: Chen, B., MacAlpine, H. K., Hartemink, A. J., MacAlpine, D. M. Tags: RESEARCH Source Type: research
Cohesin and CTCF do not assemble TADs in Xenopus sperm and male pronuclei [RESEARCH]
Paternal genomes are compacted during spermiogenesis and decompacted following fertilization. These processes are fundamental for inheritance but incompletely understood. We analyzed these processes in the frog Xenopus laevis, whose sperm can be assembled into functional pronuclei in egg extracts in vitro. In such extracts, cohesin extrudes DNA into loops, but in vivo cohesin only assembles topologically associating domains (TADs) at the mid-blastula transition (MBT). Why cohesin assembles TADs only at this stage is unknown. We first analyzed genome architecture in frog sperm and compared it to human and mouse. Our results...
Source: Genome Research - December 27, 2023 Category: Genetics & Stem Cells Authors: Jessberger, G., Varnai, C., Stocsits, R. R., Tang, W., Stary, G., Peters, J.-M. Tags: RESEARCH Source Type: research
Revisiting chromatin packaging in mouse sperm [RESEARCH]
Mammalian sperm show an unusual and heavily compacted genomic packaging state. In addition to its role in organizing the compact and hydrodynamic sperm head, it has been proposed that sperm chromatin architecture helps to program gene expression in the early embryo. Scores of genome-wide surveys in sperm have reported patterns of chromatin accessibility, nucleosome localization, histone modification, and chromosome folding. Here, we revisit these studies in light of recent reports that sperm obtained from the mouse epididymis are contaminated with low levels of cell-free chromatin. In the absence of proper sperm lysis, we ...
Source: Genome Research - December 27, 2023 Category: Genetics & Stem Cells Authors: Yin, Q., Yang, C.-H., Strelkova, O. S., Wu, J., Sun, Y., Gopalan, S., Yang, L., Dekker, J., Fazzio, T. G., Li, X. Z., Gibcus, J., Rando, O. J. Tags: RESEARCH Source Type: research
De novo transcriptome assembly of mouse male germ cells reveals novel genes, stage-specific bidirectional promoter activity, and noncoding RNA expression [RESEARCH]
In mammals, the adult testis is the tissue with the highest diversity in gene expression. Much of that diversity is attributed to germ cells, primarily meiotic spermatocytes and postmeiotic haploid spermatids. Exploiting a newly developed cell purification method, we profiled the transcriptomes of such postmitotic germ cells of mice. We used a de novo transcriptome assembly approach and identified thousands of novel expressed transcripts characterized by features distinct from those of known genes. Novel loci tend to be short in length, monoexonic, and lowly expressed. Most novel genes have arisen recently in evolutionary ...
Source: Genome Research - December 27, 2023 Category: Genetics & Stem Cells Authors: Gill, M. E., Rohmer, A., Erkek-Ozhan, S., Liang, C.-Y., Chun, S., Ozonov, E. A., Peters, A. H. F. M. Tags: RESEARCH Source Type: research
A naturally occurring variant of MBD4 causes maternal germline hypermutation in primates [RESEARCH]
As part of an ongoing genome sequencing project at the Oregon National Primate Research Center, we identified a rhesus macaque with a rare homozygous frameshift mutation in the gene methyl-CpG binding domain 4, DNA glycosylase (MBD4). MBD4 is responsible for the repair of C > T deamination mutations at CpG dinucleotides and has been linked to somatic hypermutation and cancer predisposition in humans. We show here that MBD4-associated hypermutation also affects the germline: The six offspring of the MBD4-null dam have a fourfold to sixfold increase in de novo mutation burden. This excess burden was predominantly C > T...
Source: Genome Research - December 27, 2023 Category: Genetics & Stem Cells Authors: Stendahl, A. M., Sanghvi, R., Peterson, S., Ray, K., Lima, A. C., Rahbari, R., Conrad, D. F. Tags: RESEARCH Source Type: research
A DNA methylation haplotype block landscape in human tissues and preimplantation embryos reveals regulatory elements defined by comethylation patterns [RESEARCH]
DNA methylation and associated regulatory elements play a crucial role in gene expression regulation. Previous studies have focused primarily on the distribution of mean methylation levels. Advances in whole-genome bisulfite sequencing (WGBS) have enabled the characterization of DNA methylation haplotypes (MHAPs), representing CpG sites from the same read fragment on a single chromosome, and the subsequent identification of methylation haplotype blocks (MHBs), in which adjacent CpGs on the same fragment are comethylated. Using our expert-curated WGBS data sets, we report comprehensive landscapes of MHBs in 17 representativ...
Source: Genome Research - December 27, 2023 Category: Genetics & Stem Cells Authors: Feng, Y., Zhang, Z., Hong, Y., Ding, Y., Liu, L., Gao, S., Fang, H., Shi, J. Tags: RESEARCH Source Type: research
Whole-genome long-read sequencing downsampling and its effect on variant-calling precision and recall [RESEARCH]
Advances in long-read sequencing (LRS) technologies continue to make whole-genome sequencing more complete, affordable, and accurate. LRS provides significant advantages over short-read sequencing approaches, including phased de novo genome assembly, access to previously excluded genomic regions, and discovery of more complex structural variants (SVs) associated with disease. Limitations remain with respect to cost, scalability, and platform-dependent read accuracy and the tradeoffs between sequence coverage and sensitivity of variant discovery are important experimental considerations for the application of LRS. We compar...
Source: Genome Research - December 27, 2023 Category: Genetics & Stem Cells Authors: Harvey, W. T., Ebert, P., Ebler, J., Audano, P. A., Munson, K. M., Hoekzema, K., Porubsky, D., Beck, C. R., Marschall, T., Garimella, K., Eichler, E. E. Tags: RESEARCH Source Type: research
Characterization of the distribution and dynamics of chromatin states in the C. elegans germ line reveals substantial H3K4me3 remodeling during oogenesis [RESEARCH]
Chromatin organization in the C. elegans germ line is tightly regulated and critical for germ cell differentiation. While certain germline epigenetic regulatory mechanisms have been identified, how they influence chromatin structure and ultimately gene expression remains unclear, in part because most genomic studies have focused on data collected from intact worms comprising both somatic and germline tissues. We therefore analyzed histone modification and chromatin accessibility data from isolated germ nuclei representing undifferentiated proliferating and meiosis I populations to define chromatin states. We correlated the...
Source: Genome Research - December 26, 2023 Category: Genetics & Stem Cells Authors: Mazzetto, M., Gonzalez, L. E., Sanchez, N., Reinke, V. Tags: RESEARCH Source Type: research
Revisiting chromatin packaging in mouse sperm [RESEARCH]
Mammalian sperm show an unusual and heavily compacted genomic packaging state. In addition to its role in organizing the compact and hydrodynamic sperm head, it has been proposed that sperm chromatin architecture helps to program gene expression in the early embryo. Scores of genome-wide surveys in sperm have reported patterns of chromatin accessibility, nucleosome localization, histone modification, and chromosome folding. Here, we revisit these studies in light of recent reports that sperm obtained from the mouse epididymis are contaminated with low levels of cell-free chromatin. In the absence of proper sperm lysis, we ...
Source: Genome Research - December 21, 2023 Category: Genetics & Stem Cells Authors: Yin, Q., Yang, C.-H., Strelkova, O. S., Wu, J., Sun, Y., Gopalan, S., Yang, L., Dekker, J., Fazzio, T. G., Li, X. Z., Gibcus, J., Rando, O. J. Tags: RESEARCH Source Type: research
Cohesin and CTCF do not assemble TADs in Xenopus sperm and male pronuclei [RESEARCH]
Paternal genomes are compacted during spermiogenesis and decompacted following fertilization. These processes are fundamental for inheritance but incompletely understood. We analyzed these processes in the frog Xenopus laevis, whose sperm can be assembled into functional pronuclei in egg extracts in vitro. In such extracts, cohesin extrudes DNA into loops, but in vivo cohesin only assembles topologically associating domains (TADs) at the mid-blastula transition (MBT). Why cohesin assembles TADs only at this stage is unknown. We first analyzed genome architecture in frog sperm and compared it to human and mouse. Our results...
Source: Genome Research - December 21, 2023 Category: Genetics & Stem Cells Authors: Jessberger, G., Varnai, C., Stocsits, R. R., Tang, W., Stary, G., Peters, J.-M. Tags: RESEARCH Source Type: research
De novo transcriptome assembly of mouse male germ cells reveals novel genes, stage-specific bidirectional promoter activity, and noncoding RNA expression [RESEARCH]
In mammals, the adult testis is the tissue with the highest diversity in gene expression. Much of that diversity is attributed to germ cells, primarily meiotic spermatocytes and postmeiotic haploid spermatids. Exploiting a newly developed cell purification method, we profiled the transcriptomes of such postmitotic germ cells of mice. We used a de novo transcriptome assembly approach and identified thousands of novel expressed transcripts characterized by features distinct from those of known genes. Novel loci tend to be short in length, monoexonic, and lowly expressed. Most novel genes have arisen recently in evolutionary ...
Source: Genome Research - December 21, 2023 Category: Genetics & Stem Cells Authors: Gill, M. E., Rohmer, A., Erkek-Ozhan, S., Liang, C.-Y., Chun, S., Ozonov, E. A., Peters, A. H. F. M. Tags: RESEARCH Source Type: research
Data integration and inference of gene regulation using single-cell temporal multimodal data with scTIE [METHOD]
Single-cell technologies offer unprecedented opportunities to dissect gene regulatory mechanisms in context-specific ways. Although there are computational methods for extracting gene regulatory relationships from scRNA-seq and scATAC-seq data, the data integration problem, essential for accurate cell type identification, has been mostly treated as a standalone challenge. Here we present scTIE, a unified method that integrates temporal multimodal data and infers regulatory relationships predictive of cellular state changes. scTIE uses an autoencoder to embed cells from all time points into a common space using iterative op...
Source: Genome Research - December 15, 2023 Category: Genetics & Stem Cells Authors: Lin, Y., Wu, T.-Y., Chen, X., Wan, S., Chao, B., Xin, J., Yang, J., Wong, W. H., Wang, Y. X. R. Tags: METHOD Source Type: research
