Genome BiologyPub Date : 2022-10-12DOI: 10.1186/s13059-022-02782-z
Seonghyun Lee, Hyunji Lee, Gayoung Baek, Eunji Namgung, Joo Min Park, Sanghun Kim, Seongho Hong, Jin-Soo Kim
{"title":"Enhanced mitochondrial DNA editing in mice using nuclear-exported TALE-linked deaminases and nucleases.","authors":"Seonghyun Lee, Hyunji Lee, Gayoung Baek, Eunji Namgung, Joo Min Park, Sanghun Kim, Seongho Hong, Jin-Soo Kim","doi":"10.1186/s13059-022-02782-z","DOIUrl":"10.1186/s13059-022-02782-z","url":null,"abstract":"<p><p>We present two methods for enhancing the efficiency of mitochondrial DNA (mtDNA) editing in mice with DddA-derived cytosine base editors (DdCBEs). First, we fused DdCBEs to a nuclear export signal (DdCBE-NES) to avoid off-target C-to-T conversions in the nuclear genome and improve editing efficiency in mtDNA. Second, mtDNA-targeted TALENs (mitoTALENs) are co-injected into mouse embryos to cleave unedited mtDNA. We generated a mouse model with the m.G12918A mutation in the MT-ND5 gene, associated with mitochondrial genetic disorders in humans. The mutant mice show hunched appearances, damaged mitochondria in kidney and brown adipose tissues, and hippocampal atrophy, resulting in premature death.</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"23 1","pages":"211"},"PeriodicalIF":12.3,"publicationDate":"2022-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9554978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33503033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome BiologyPub Date : 2022-10-04DOI: 10.1186/s13059-022-02771-2
Ivar Grytten, Knut Dagestad Rand, Geir Kjetil Sandve
{"title":"KAGE: fast alignment-free graph-based genotyping of SNPs and short indels.","authors":"Ivar Grytten, Knut Dagestad Rand, Geir Kjetil Sandve","doi":"10.1186/s13059-022-02771-2","DOIUrl":"https://doi.org/10.1186/s13059-022-02771-2","url":null,"abstract":"<p><p>Genotyping is a core application of high-throughput sequencing. We present KAGE, a genotyper for SNPs and short indels that is inspired by recent developments within graph-based genome representations and alignment-free methods. KAGE uses a pan-genome representation of the population to efficiently and accurately predict genotypes. Two novel ideas improve both the speed and accuracy: a Bayesian model incorporates genotypes from thousands of individuals to improve prediction accuracy, and a computationally efficient method leverages correlation between variants. We show that the accuracy of KAGE is at par with the best existing alignment-free genotypers, while being an order of magnitude faster.</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"23 1","pages":"209"},"PeriodicalIF":12.3,"publicationDate":"2022-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9531401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33489028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome BiologyPub Date : 2022-10-03DOI: 10.1186/s13059-022-02775-y
Eva Galle, Chee-Wai Wong, Adhideb Ghosh, Thibaut Desgeorges, Kate Melrose, Laura C Hinte, Daniel Castellano-Castillo, Magdalena Engl, Joao Agostinho de Sousa, Francisco Javier Ruiz-Ojeda, Katrien De Bock, Jonatan R Ruiz, Ferdinand von Meyenn
{"title":"H3K18 lactylation marks tissue-specific active enhancers.","authors":"Eva Galle, Chee-Wai Wong, Adhideb Ghosh, Thibaut Desgeorges, Kate Melrose, Laura C Hinte, Daniel Castellano-Castillo, Magdalena Engl, Joao Agostinho de Sousa, Francisco Javier Ruiz-Ojeda, Katrien De Bock, Jonatan R Ruiz, Ferdinand von Meyenn","doi":"10.1186/s13059-022-02775-y","DOIUrl":"https://doi.org/10.1186/s13059-022-02775-y","url":null,"abstract":"<p><strong>Background: </strong>Histone lactylation has been recently described as a novel histone post-translational modification linking cellular metabolism to epigenetic regulation.</p><p><strong>Results: </strong>Given the expected relevance of this modification and current limited knowledge of its function, we generate genome-wide datasets of H3K18la distribution in various in vitro and in vivo samples, including mouse embryonic stem cells, macrophages, adipocytes, and mouse and human skeletal muscle. We compare them to profiles of well-established histone modifications and gene expression patterns. Supervised and unsupervised bioinformatics analysis shows that global H3K18la distribution resembles H3K27ac, although we also find notable differences. H3K18la marks active CpG island-containing promoters of highly expressed genes across most tissues assessed, including many housekeeping genes, and positively correlates with H3K27ac and H3K4me3 as well as with gene expression. In addition, H3K18la is enriched at active enhancers that lie in proximity to genes that are functionally important for the respective tissue.</p><p><strong>Conclusions: </strong>Overall, our data suggests that H3K18la is not only a marker for active promoters, but also a mark of tissue specific active enhancers.</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"23 1","pages":"207"},"PeriodicalIF":12.3,"publicationDate":"2022-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9531456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33486751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome BiologyPub Date : 2022-09-23DOI: 10.1186/s13059-022-02769-w
Deyan Wang, Yiling Li, Mengmeng Li, Wenlu Yang, Xinzhi Ma, Lei Zhang, Yubo Wang, Yanlin Feng, Yuanyuan Zhang, Ran Zhou, Brian J Sanderson, Ken Keefover-Ring, Tongming Yin, Lawrence B Smart, Stephen P DiFazio, Jianquan Liu, Matthew Olson, Tao Ma
{"title":"Repeated turnovers keep sex chromosomes young in willows.","authors":"Deyan Wang, Yiling Li, Mengmeng Li, Wenlu Yang, Xinzhi Ma, Lei Zhang, Yubo Wang, Yanlin Feng, Yuanyuan Zhang, Ran Zhou, Brian J Sanderson, Ken Keefover-Ring, Tongming Yin, Lawrence B Smart, Stephen P DiFazio, Jianquan Liu, Matthew Olson, Tao Ma","doi":"10.1186/s13059-022-02769-w","DOIUrl":"https://doi.org/10.1186/s13059-022-02769-w","url":null,"abstract":"<p><strong>Background: </strong>Salicaceae species have diverse sex determination systems and frequent sex chromosome turnovers. However, compared with poplars, the diversity of sex determination in willows is poorly understood, and little is known about the evolutionary forces driving their turnover. Here, we characterized the sex determination in two Salix species, S. chaenomeloides and S. arbutifolia, which have an XY system on chromosome 7 and 15, respectively.</p><p><strong>Results: </strong>Based on the assemblies of their sex determination regions, we found that the sex determination mechanism of willows may have underlying similarities with poplars, both involving intact and/or partial homologs of a type A cytokinin response regulator (RR) gene. Comparative analyses suggested that at least two sex turnover events have occurred in Salix, one preserving the ancestral pattern of male heterogamety, and the other changing heterogametic sex from XY to ZW, which could be partly explained by the \"deleterious mutation load\" and \"sexually antagonistic selection\" theoretical models. We hypothesize that these repeated turnovers keep sex chromosomes of willow species in a perpetually young state, leading to limited degeneration.</p><p><strong>Conclusions: </strong>Our findings further improve the evolutionary trajectory of sex chromosomes in Salicaceae species, explore the evolutionary forces driving the repeated turnovers of their sex chromosomes, and provide a valuable reference for the study of sex chromosomes in other species.</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"23 1","pages":"200"},"PeriodicalIF":12.3,"publicationDate":"2022-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9502649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33479701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome BiologyPub Date : 2022-09-12DOI: 10.1186/s13059-022-02759-y
Berta Duran-Arqué, Manuel Cañete, Chiara Lara Castellazzi, Anna Bartomeu, Anna Ferrer-Caelles, Oscar Reina, Adrià Caballé, Marina Gay, Gianluca Arauz-Garofalo, Eulalia Belloc, Raúl Mendez
{"title":"Comparative analyses of vertebrate CPEB proteins define two subfamilies with coordinated yet distinct functions in post-transcriptional gene regulation.","authors":"Berta Duran-Arqué, Manuel Cañete, Chiara Lara Castellazzi, Anna Bartomeu, Anna Ferrer-Caelles, Oscar Reina, Adrià Caballé, Marina Gay, Gianluca Arauz-Garofalo, Eulalia Belloc, Raúl Mendez","doi":"10.1186/s13059-022-02759-y","DOIUrl":"10.1186/s13059-022-02759-y","url":null,"abstract":"<p><strong>Background: </strong>Vertebrate CPEB proteins bind mRNAs at cytoplasmic polyadenylation elements (CPEs) in their 3' UTRs, leading to cytoplasmic changes in their poly(A) tail lengths; this can promote translational repression or activation of the mRNA. However, neither the regulation nor the mechanisms of action of the CPEB family per se have been systematically addressed to date.</p><p><strong>Results: </strong>Based on a comparative analysis of the four vertebrate CPEBs, we determine their differential regulation by phosphorylation, the composition and properties of their supramolecular assemblies, and their target mRNAs. We show that all four CPEBs are able to recruit the CCR4-NOT deadenylation complex to repress the translation. However, their regulation, mechanism of action, and target mRNAs define two subfamilies. Thus, CPEB1 forms ribonucleoprotein complexes that are remodeled upon a single phosphorylation event and are associated with mRNAs containing canonical CPEs. CPEB2-4 are regulated by multiple proline-directed phosphorylations that control their liquid-liquid phase separation. CPEB2-4 mRNA targets include CPEB1-bound transcripts, with canonical CPEs, but also a specific subset of mRNAs with non-canonical CPEs.</p><p><strong>Conclusions: </strong>Altogether, these results show how, globally, the CPEB family of proteins is able to integrate cellular cues to generate a fine-tuned adaptive response in gene expression regulation through the coordinated actions of all four members.</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"23 1","pages":"192"},"PeriodicalIF":12.3,"publicationDate":"2022-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9465852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33463627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome BiologyPub Date : 2022-09-12DOI: 10.1186/s13059-022-02760-5
Fabian Poetz, Svetlana Lebedeva, Johanna Schott, Doris Lindner, Uwe Ohler, Georg Stoecklin
{"title":"Control of immediate early gene expression by CPEB4-repressor complex-mediated mRNA degradation.","authors":"Fabian Poetz, Svetlana Lebedeva, Johanna Schott, Doris Lindner, Uwe Ohler, Georg Stoecklin","doi":"10.1186/s13059-022-02760-5","DOIUrl":"10.1186/s13059-022-02760-5","url":null,"abstract":"<p><strong>Background: </strong>Cytoplasmic polyadenylation element-binding protein 4 (CPEB4) is known to associate with cytoplasmic polyadenylation elements (CPEs) located in the 3' untranslated region (UTR) of specific mRNAs and assemble an activator complex promoting the translation of target mRNAs through cytoplasmic polyadenylation.</p><p><strong>Results: </strong>Here, we find that CPEB4 is part of an alternative repressor complex that mediates mRNA degradation by associating with the evolutionarily conserved CCR4-NOT deadenylase complex. We identify human CPEB4 as an RNA-binding protein (RBP) with enhanced association to poly(A) RNA upon inhibition of class I histone deacetylases (HDACs), a condition known to cause widespread degradation of poly(A)-containing mRNA. Photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) analysis using endogenously tagged CPEB4 in HeLa cells reveals that CPEB4 preferentially binds to the 3'UTR of immediate early gene mRNAs, at G-containing variants of the canonical U- and A-rich CPE located in close proximity to poly(A) sites. By transcriptome-wide mRNA decay measurements, we find that the strength of CPEB4 binding correlates with short mRNA half-lives and that loss of CPEB4 expression leads to the stabilization of immediate early gene mRNAs. Akin to CPEB4, we demonstrate that CPEB1 and CPEB2 also confer mRNA instability by recruitment of the CCR4-NOT complex.</p><p><strong>Conclusions: </strong>While CPEB4 was previously known for its ability to stimulate cytoplasmic polyadenylation, our findings establish an additional function for CPEB4 as the RNA adaptor of a repressor complex that enhances the degradation of short-lived immediate early gene mRNAs.</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"23 1","pages":"193"},"PeriodicalIF":12.3,"publicationDate":"2022-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9465963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33470614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome BiologyPub Date : 2022-09-09DOI: 10.1186/s13059-022-02755-2
Klara Kuret, Aram Gustav Amalietti, D Marc Jones, Charlotte Capitanchik, Jernej Ule
{"title":"Positional motif analysis reveals the extent of specificity of protein-RNA interactions observed by CLIP.","authors":"Klara Kuret, Aram Gustav Amalietti, D Marc Jones, Charlotte Capitanchik, Jernej Ule","doi":"10.1186/s13059-022-02755-2","DOIUrl":"10.1186/s13059-022-02755-2","url":null,"abstract":"<p><strong>Background: </strong>Crosslinking and immunoprecipitation (CLIP) is a method used to identify in vivo RNA-protein binding sites on a transcriptome-wide scale. With the increasing amounts of available data for RNA-binding proteins (RBPs), it is important to understand to what degree the enriched motifs specify the RNA-binding profiles of RBPs in cells.</p><p><strong>Results: </strong>We develop positionally enriched k-mer analysis (PEKA), a computational tool for efficient analysis of enriched motifs from individual CLIP datasets, which minimizes the impact of technical and regional genomic biases by internal data normalization. We cross-validate PEKA with mCross and show that the use of input control for background correction is not required to yield high specificity of enriched motifs. We identify motif classes with common enrichment patterns across eCLIP datasets and across RNA regions, while also observing variations in the specificity and the extent of motif enrichment across eCLIP datasets, between variant CLIP protocols, and between CLIP and in vitro binding data. Thereby, we gain insights into the contributions of technical and regional genomic biases to the enriched motifs, and find how motif enrichment features relate to the domain composition and low-complexity regions of the studied proteins.</p><p><strong>Conclusions: </strong>Our study provides insights into the overall contributions of regional binding preferences, protein domains, and low-complexity regions to the specificity of protein-RNA interactions, and shows the value of cross-motif and cross-RBP comparison for data interpretation. Our results are presented for exploratory analysis via an online platform in an RBP-centric and motif-centric manner ( https://imaps.goodwright.com/apps/peka/ ).</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"23 1","pages":"191"},"PeriodicalIF":12.3,"publicationDate":"2022-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9461102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33460725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome BiologyPub Date : 2022-09-08DOI: 10.1186/s13059-022-02743-6
Jamshed Khan, Marek Kokot, Sebastian Deorowicz, Rob Patro
{"title":"Scalable, ultra-fast, and low-memory construction of compacted de Bruijn graphs with Cuttlefish 2.","authors":"Jamshed Khan, Marek Kokot, Sebastian Deorowicz, Rob Patro","doi":"10.1186/s13059-022-02743-6","DOIUrl":"10.1186/s13059-022-02743-6","url":null,"abstract":"<p><p>The de Bruijn graph is a key data structure in modern computational genomics, and construction of its compacted variant resides upstream of many genomic analyses. As the quantity of genomic data grows rapidly, this often forms a computational bottleneck. We present Cuttlefish 2, significantly advancing the state-of-the-art for this problem. On a commodity server, it reduces the graph construction time for 661K bacterial genomes, of size 2.58Tbp, from 4.5 days to 17-23 h; and it constructs the graph for 1.52Tbp white spruce reads in approximately 10 h, while the closest competitor requires 54-58 h, using considerably more memory.</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"23 1","pages":"190"},"PeriodicalIF":12.3,"publicationDate":"2022-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9454175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33453631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome BiologyPub Date : 2022-09-07DOI: 10.1186/s13059-022-02756-1
Ningyang Li, Xueyu Zhang, Xiudong Sun, Siyuan Zhu, Yi Cheng, Meng Liu, Song Gao, Jiangjiang Zhang, Yanzhou Wang, Xiai Yang, Jianrong Chen, Fu Li, Qiaoyun He, Zheng Zeng, Xiaoge Yuan, Zhiman Zhou, Longchuan Ma, Taotao Wang, Xiang Li, Hanqiang Liu, Yupeng Pan, Mengyan Zhou, Chunsheng Gao, Gang Zhou, Zhenlin Han, Shiqi Liu, Jianguang Su, Zhihui Cheng, Shilin Tian, Touming Liu
{"title":"Genomic insights into the evolutionary history and diversification of bulb traits in garlic.","authors":"Ningyang Li, Xueyu Zhang, Xiudong Sun, Siyuan Zhu, Yi Cheng, Meng Liu, Song Gao, Jiangjiang Zhang, Yanzhou Wang, Xiai Yang, Jianrong Chen, Fu Li, Qiaoyun He, Zheng Zeng, Xiaoge Yuan, Zhiman Zhou, Longchuan Ma, Taotao Wang, Xiang Li, Hanqiang Liu, Yupeng Pan, Mengyan Zhou, Chunsheng Gao, Gang Zhou, Zhenlin Han, Shiqi Liu, Jianguang Su, Zhihui Cheng, Shilin Tian, Touming Liu","doi":"10.1186/s13059-022-02756-1","DOIUrl":"https://doi.org/10.1186/s13059-022-02756-1","url":null,"abstract":"<p><strong>Background: </strong>Garlic is an entirely sterile crop with important value as a vegetable, condiment, and medicine. However, the evolutionary history of garlic remains largely unknown.</p><p><strong>Results: </strong>Here we report a comprehensive map of garlic genomic variation, consisting of amazingly 129.4 million variations. Evolutionary analysis indicates that the garlic population diverged at least 100,000 years ago, and the two groups cultivated in China were domesticated from two independent routes. Consequently, 15.0 and 17.5% of genes underwent an expression change in two cultivated groups, causing a reshaping of their transcriptomic architecture. Furthermore, we find independent domestication leads to few overlaps of deleterious substitutions in these two groups due to separate accumulation and selection-based removal. By analysis of selective sweeps, genome-wide trait associations and associated transcriptomic analysis, we uncover differential selections for the bulb traits in these two garlic groups during their domestication.</p><p><strong>Conclusions: </strong>This study provides valuable resources for garlic genomics-based breeding, and comprehensive insights into the evolutionary history of this clonal-propagated crop.</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"23 1","pages":"188"},"PeriodicalIF":12.3,"publicationDate":"2022-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9450234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33448119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}