Genome Biology最新文献_第4页

The Arabidopsis APOLO and human UPAT sequence-unrelated long noncoding RNAs can modulate DNA and histone methylation machineries in plants. 拟南芥APOLO和人类UPAT序列无关的长链非编码rna可以调节植物DNA和组蛋白甲基化机制。

IF 12.3 1区生物学

Genome Biology Pub Date : 2022-08-29 DOI: 10.1186/s13059-022-02750-7

Camille Fonouni-Farde, Aurélie Christ, Thomas Blein, María Florencia Legascue, Lucía Ferrero, Michaël Moison, Leandro Lucero, Juan Sebastián Ramírez-Prado, David Latrasse, Daniel Gonzalez, Moussa Benhamed, Leandro Quadrana, Martin Crespi, Federico Ariel

{"title":"The Arabidopsis APOLO and human UPAT sequence-unrelated long noncoding RNAs can modulate DNA and histone methylation machineries in plants.","authors":"Camille Fonouni-Farde, Aurélie Christ, Thomas Blein, María Florencia Legascue, Lucía Ferrero, Michaël Moison, Leandro Lucero, Juan Sebastián Ramírez-Prado, David Latrasse, Daniel Gonzalez, Moussa Benhamed, Leandro Quadrana, Martin Crespi, Federico Ariel","doi":"10.1186/s13059-022-02750-7","DOIUrl":"https://doi.org/10.1186/s13059-022-02750-7","url":null,"abstract":"Background: RNA-DNA hybrid (R-loop)-associated long noncoding RNAs (lncRNAs), including the Arabidopsis lncRNA AUXIN-REGULATED PROMOTER LOOP (APOLO), are emerging as important regulators of three-dimensional chromatin conformation and gene transcriptional activity.Results: Here, we show that in addition to the PRC1-component LIKE HETEROCHROMATIN PROTEIN 1 (LHP1), APOLO interacts with the methylcytosine-binding protein VARIANT IN METHYLATION 1 (VIM1), a conserved homolog of the mammalian DNA methylation regulator UBIQUITIN-LIKE CONTAINING PHD AND RING FINGER DOMAINS 1 (UHRF1). The APOLO-VIM1-LHP1 complex directly regulates the transcription of the auxin biosynthesis gene YUCCA2 by dynamically determining DNA methylation and H3K27me3 deposition over its promoter during the plant thermomorphogenic response. Strikingly, we demonstrate that the lncRNA UHRF1 Protein Associated Transcript (UPAT), a direct interactor of UHRF1 in humans, can be recognized by VIM1 and LHP1 in plant cells, despite the lack of sequence homology between UPAT and APOLO. In addition, we show that increased levels of APOLO or UPAT hamper VIM1 and LHP1 binding to YUCCA2 promoter and globally alter the Arabidopsis transcriptome in a similar manner.Conclusions: Collectively, our results uncover a new mechanism in which a plant lncRNA coordinates Polycomb action and DNA methylation through the interaction with VIM1, and indicates that evolutionary unrelated lncRNAs with potentially conserved structures may exert similar functions by interacting with homolog partners.","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"23 1","pages":"181"},"PeriodicalIF":12.3,"publicationDate":"2022-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9422110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33446687","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}

引用次数: 8

Multiple genome alignment in the telomere-to-telomere assembly era. 端粒与端粒组装时代的多基因组比对。

IF 12.3 1区生物学

Genome Biology Pub Date : 2022-08-29 DOI: 10.1186/s13059-022-02735-6

Bryce Kille, Advait Balaji, Fritz J Sedlazeck, Michael Nute, Todd J Treangen

引用次数: 13

Modeling zero inflation is not necessary for spatial transcriptomics. 空间转录组学并不需要建立零膨胀模型。

IF 12.3 1区生物学

Genome Biology Pub Date : 2022-05-18 DOI: 10.1186/s13059-022-02684-0

Peiyao Zhao, Jiaqiang Zhu, Ying Ma, Xiang Zhou

{"title":"Modeling zero inflation is not necessary for spatial transcriptomics.","authors":"Peiyao Zhao, Jiaqiang Zhu, Ying Ma, Xiang Zhou","doi":"10.1186/s13059-022-02684-0","DOIUrl":"https://doi.org/10.1186/s13059-022-02684-0","url":null,"abstract":"Background: Spatial transcriptomics are a set of new technologies that profile gene expression on tissues with spatial localization information. With technological advances, recent spatial transcriptomics data are often in the form of sparse counts with an excessive amount of zero values.Results: We perform a comprehensive analysis on 20 spatial transcriptomics datasets collected from 11 distinct technologies to characterize the distributional properties of the expression count data and understand the statistical nature of the zero values. Across datasets, we show that a substantial fraction of genes displays overdispersion and/or zero inflation that cannot be accounted for by a Poisson model, with genes displaying overdispersion substantially overlapped with genes displaying zero inflation. In addition, we find that either the Poisson or the negative binomial model is sufficient for modeling the majority of genes across most spatial transcriptomics technologies. We further show major sources of overdispersion and zero inflation in spatial transcriptomics including gene expression heterogeneity across tissue locations and spatial distribution of cell types. In particular, when we focus on a relatively homogeneous set of tissue locations or control for cell type compositions, the number of detected overdispersed and/or zero-inflated genes is substantially reduced, and a simple Poisson model is often sufficient to fit the gene expression data there.Conclusions: Our study provides the first comprehensive evidence that excessive zeros in spatial transcriptomics are not due to zero inflation, supporting the use of count models without a zero inflation component for modeling spatial transcriptomics.","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"23 1","pages":"118"},"PeriodicalIF":12.3,"publicationDate":"2022-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9116027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074282","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}

引用次数: 0

Cell type determination for cardiac differentiation occurs soon after seeding of human-induced pluripotent stem cells. 人类诱导多能干细胞播种后，很快就会确定心脏分化的细胞类型。

IF 12.3 1区生物学

Genome Biology Pub Date : 2022-04-05 DOI: 10.1186/s13059-022-02654-6

Connie L Jiang, Yogesh Goyal, Naveen Jain, Qiaohong Wang, Rachel E Truitt, Allison J Coté, Benjamin Emert, Ian A Mellis, Karun Kiani, Wenli Yang, Rajan Jain, Arjun Raj

{"title":"Cell type determination for cardiac differentiation occurs soon after seeding of human-induced pluripotent stem cells.","authors":"Connie L Jiang, Yogesh Goyal, Naveen Jain, Qiaohong Wang, Rachel E Truitt, Allison J Coté, Benjamin Emert, Ian A Mellis, Karun Kiani, Wenli Yang, Rajan Jain, Arjun Raj","doi":"10.1186/s13059-022-02654-6","DOIUrl":"10.1186/s13059-022-02654-6","url":null,"abstract":"Background: Cardiac differentiation of human-induced pluripotent stem (hiPS) cells consistently produces a mixed population of cardiomyocytes and non-cardiac cell types, even when using well-characterized protocols. We sought to determine whether different cell types might result from intrinsic differences in hiPS cells prior to the onset of differentiation.Results: By associating individual differentiated cells that share a common hiPS cell precursor, we tested whether expression variability is predetermined from the hiPS cell state. In a single experiment, cells that shared a progenitor were more transcriptionally similar to each other than to other cells in the differentiated population. However, when the same hiPS cells were differentiated in parallel, we did not observe high transcriptional similarity across differentiations. Additionally, we found that substantial cell death occurs during differentiation in a manner that suggested all cells were equally likely to survive or die, suggesting that there is no intrinsic selection bias for cells descended from particular hiPS cell progenitors. We thus wondered how cells grow spatially during differentiation, so we labeled cells by expression of marker genes and found that cells expressing the same marker tended to occur in patches. Our results suggest that cell type determination across multiple cell types, once initiated, is maintained in a cell-autonomous manner for multiple divisions.Conclusions: Altogether, our results show that while substantial heterogeneity exists in the initial hiPS cell population, it is not responsible for the variability observed in differentiated outcomes; instead, factors specifying the various cell types likely act during a window that begins shortly after the seeding of hiPS cells for differentiation.","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"23 1","pages":"90"},"PeriodicalIF":12.3,"publicationDate":"2022-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8985385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912393","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}

引用次数: 0

LAP2α preserves genome integrity through assisting RPA deposition on damaged chromatin. LAP2α 通过协助 RPA 在受损染色质上的沉积来维护基因组的完整性。

IF 12.3 1区生物学

Genome Biology Pub Date : 2022-02-28 DOI: 10.1186/s13059-022-02638-6

Kaiwen Bao, Qi Zhang, Shuai Liu, Nan Song, Qiushi Guo, Ling Liu, Shanshan Tian, Jihui Hao, Yi Zhu, Kai Zhang, Ding Ai, Jie Yang, Zhi Yao, Roland Foisner, Lei Shi

{"title":"LAP2α preserves genome integrity through assisting RPA deposition on damaged chromatin.","authors":"Kaiwen Bao, Qi Zhang, Shuai Liu, Nan Song, Qiushi Guo, Ling Liu, Shanshan Tian, Jihui Hao, Yi Zhu, Kai Zhang, Ding Ai, Jie Yang, Zhi Yao, Roland Foisner, Lei Shi","doi":"10.1186/s13059-022-02638-6","DOIUrl":"10.1186/s13059-022-02638-6","url":null,"abstract":"Background: Single-stranded DNA (ssDNA) coated with replication protein A (RPA) acts as a key platform for the recruitment and exchange of genome maintenance factors in DNA damage response. Yet, how the formation of the ssDNA-RPA intermediate is regulated remains elusive.Results: Here, we report that the lamin-associated protein LAP2α is physically associated with RPA, and LAP2α preferentially facilitates RPA deposition on damaged chromatin via physical contacts between LAP2α and RPA1. Importantly, LAP2α-promoted RPA binding to ssDNA plays a critical role in protection of replication forks, activation of ATR, and repair of damaged DNA. We further demonstrate that the preference of LAP2α-promoted RPA loading on damaged chromatin depends on poly ADP-ribose polymerase PARP1, but not poly(ADP-ribosyl)ation.Conclusions: Our study provides mechanistic insight into RPA deposition in response to DNA damage and reveals a genome protection role of LAP2α.","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"23 1","pages":"64"},"PeriodicalIF":12.3,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307233","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}

引用次数: 0

Comparative regulomics supports pervasive selection on gene dosage following whole genome duplication. 比较调控组学支持全基因组复制后对基因剂量的普遍选择。

IF 12.3 1区生物学

Genome Biology Pub Date : 2021-04-13 DOI: 10.1186/s13059-021-02323-0

Gareth B Gillard, Lars Grønvold, Line L Røsæg, Matilde Mengkrog Holen, Øystein Monsen, Ben F Koop, Eric B Rondeau, Manu Kumar Gundappa, John Mendoza, Daniel J Macqueen, Rori V Rohlfs, Simen R Sandve, Torgeir R Hvidsten

{"title":"Comparative regulomics supports pervasive selection on gene dosage following whole genome duplication.","authors":"Gareth B Gillard, Lars Grønvold, Line L Røsæg, Matilde Mengkrog Holen, Øystein Monsen, Ben F Koop, Eric B Rondeau, Manu Kumar Gundappa, John Mendoza, Daniel J Macqueen, Rori V Rohlfs, Simen R Sandve, Torgeir R Hvidsten","doi":"10.1186/s13059-021-02323-0","DOIUrl":"10.1186/s13059-021-02323-0","url":null,"abstract":"Background: Whole genome duplication (WGD) events have played a major role in eukaryotic genome evolution, but the consequence of these extreme events in adaptive genome evolution is still not well understood. To address this knowledge gap, we used a comparative phylogenetic model and transcriptomic data from seven species to infer selection on gene expression in duplicated genes (ohnologs) following the salmonid WGD 80-100 million years ago.Results: We find rare cases of tissue-specific expression evolution but pervasive expression evolution affecting many tissues, reflecting strong selection on maintenance of genome stability following genome doubling. Ohnolog expression levels have evolved mostly asymmetrically, by diverting one ohnolog copy down a path towards lower expression and possible pseudogenization. Loss of expression in one ohnolog is significantly associated with transposable element insertions in promoters and likely driven by selection on gene dosage including selection on stoichiometric balance. We also find symmetric expression shifts, and these are associated with genes under strong evolutionary constraints such as ribosome subunit genes. This possibly reflects selection operating to achieve a gene dose reduction while avoiding accumulation of \"toxic mutations\". Mechanistically, ohnolog regulatory divergence is dictated by the number of bound transcription factors in promoters, with transposable elements being one likely source of novel binding sites driving tissue-specific gains in expression.Conclusions: Our results imply pervasive adaptive expression evolution following WGD to overcome the immediate challenges posed by genome doubling and to exploit the long-term genetic opportunities for novel phenotype evolution.","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"22 1","pages":"103"},"PeriodicalIF":12.3,"publicationDate":"2021-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25585826","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}

引用次数: 0

PD-L1 lncRNA splice isoform promotes lung adenocarcinoma progression via enhancing c-Myc activity. PD-L1 lncRNA剪接异构体通过增强c-Myc的活性促进肺腺癌的进展。

IF 12.3 1区生物学

Genome Biology Pub Date : 2021-04-13 DOI: 10.1186/s13059-021-02331-0

Shuang Qu, Zichen Jiao, Geng Lu, Bing Yao, Ting Wang, Weiwei Rong, Jiahan Xu, Ting Fan, Xinlei Sun, Rong Yang, Jun Wang, Yongzhong Yao, Guifang Xu, Xin Yan, Tao Wang, Hongwei Liang, Ke Zen

{"title":"PD-L1 lncRNA splice isoform promotes lung adenocarcinoma progression via enhancing c-Myc activity.","authors":"Shuang Qu, Zichen Jiao, Geng Lu, Bing Yao, Ting Wang, Weiwei Rong, Jiahan Xu, Ting Fan, Xinlei Sun, Rong Yang, Jun Wang, Yongzhong Yao, Guifang Xu, Xin Yan, Tao Wang, Hongwei Liang, Ke Zen","doi":"10.1186/s13059-021-02331-0","DOIUrl":"10.1186/s13059-021-02331-0","url":null,"abstract":"Background: Although using a blockade of programmed death-ligand 1 (PD-L1) to enhance T cell immune responses shows great promise in tumor immunotherapy, the immune-checkpoint inhibition strategy is limited for patients with solid tumors. The mechanism and efficacy of such immune-checkpoint inhibition strategies in solid tumors remains unclear.Results: Employing qRT-PCR, Sanger sequencing, and RNA BaseScope analysis, we show that human lung adenocarcinoma (LUAD) all produce a long non-coding RNA isoform of PD-L1 (PD-L1-lnc) by alternative splicing, regardless if the tumor is positive or negative for the protein PD-L1. Similar to PD-L1 mRNA, PD-L1-lnc in various lung adenocarcinoma cells is significantly upregulated by IFNγ. Both in vitro and in vivo studies demonstrate that PD-L1-lnc increases proliferation and invasion but decreases apoptosis of lung adenocarcinoma cells. Mechanistically, PD-L1-lnc promotes lung adenocarcinoma progression through directly binding to c-Myc and enhancing c-Myc transcriptional activity.Conclusions: In summary, the PD-L1 gene can generate a long non-coding RNA through alternative splicing to promote lung adenocarcinoma progression by enhancing c-Myc activity. Our results argue in favor of investigating PD-L1-lnc depletion in combination with PD-L1 blockade in lung cancer therapy.","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"22 1","pages":"104"},"PeriodicalIF":12.3,"publicationDate":"2021-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25588666","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}

引用次数: 0

Computational methods for chromosome-scale haplotype reconstruction. 染色体尺度单倍型重建的计算方法。

IF 12.3 1区生物学

Genome Biology Pub Date : 2021-04-12 DOI: 10.1186/s13059-021-02328-9

Shilpa Garg

引用次数: 40

ACME dissociation: a versatile cell fixation-dissociation method for single-cell transcriptomics. ACME 解离法：一种用于单细胞转录组学的多功能细胞固定-解离方法。

IF 12.3 1区生物学

Genome Biology Pub Date : 2021-04-08 DOI: 10.1186/s13059-021-02302-5

Helena García-Castro, Nathan J Kenny, Marta Iglesias, Patricia Álvarez-Campos, Vincent Mason, Anamaria Elek, Anna Schönauer, Victoria A Sleight, Jakke Neiro, Aziz Aboobaker, Jon Permanyer, Manuel Irimia, Arnau Sebé-Pedrós, Jordi Solana

引用次数: 0

Response to "Reproducibility of CRISPR-Cas9 methods for generation of conditional mouse alleles: a multi-center evaluation". 对“产生条件小鼠等位基因的CRISPR-Cas9方法的可重复性:多中心评估”的回应。

IF 12.3 1区生物学

Genome Biology Pub Date : 2021-04-07 DOI: 10.1186/s13059-021-02312-3

Hui Yang, Haoyi Wang, Rudolf Jaenisch

引用次数: 2