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  • Oxford University Press (OUP)  (21)
  • Biodiversity Research  (21)
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  • Oxford University Press (OUP)  (21)
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  • Biodiversity Research  (21)
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  • 1
    Online Resource
    Online Resource
    CistromeFinder for ChIP-seq and DNase-seq data reuse
    Oxford University Press (OUP) ; 2013
    In:  Bioinformatics Vol. 29, No. 10 ( 2013-05-15), p. 1352-1354
    Details
    In: Bioinformatics, Oxford University Press (OUP), Vol. 29, No. 10 ( 2013-05-15), p. 1352-1354
    Abstract: Summary: Chromatin immunoprecipitation and DNase I hypersensitivity assays with high-throughput sequencing have greatly accelerated the understanding of transcriptional and epigenetic regulation, although data reuse for the community of experimental biologists has been challenging. We created a data portal CistromeFinder that can help query, evaluate and visualize publicly available Chromatin immunoprecipitation and DNase I hypersensitivity assays with high-throughput sequencing data in human and mouse. The database currently contains 6378 samples over 4391 datasets, 313 factors and 102 cell lines or cell populations. Each dataset has gone through a consistent analysis and quality control pipeline; therefore, users could evaluate the overall quality of each dataset before examining binding sites near their genes of interest. CistromeFinder is integrated with UCSC genome browser for visualization, Primer3Plus for ChIP-qPCR primer design and CistromeMap for submitting newly available datasets. It also allows users to leave comments to facilitate data evaluation and update. Availability:  http://cistrome.org/finder. Contact:  xsliu@jimmy.harvard.edu or henry_long@dfci.harvard.edu
    Type of Medium: Online Resource
    ISSN: 1367-4811 , 1367-4803
    URL: Article
    DOI: 10.1093/bioinformatics/btt135
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2013
    detail.hit.zdb_id: 1468345-3
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    RBBP4 is an epigenetic barrier for the induced transition of pluripotent stem cells into totipotent 2C-like cells
    Oxford University Press (OUP) ; 2023
    In:  Nucleic Acids Research Vol. 51, No. 11 ( 2023-06-23), p. 5414-5431
    Details
    In: Nucleic Acids Research, Oxford University Press (OUP), Vol. 51, No. 11 ( 2023-06-23), p. 5414-5431
    Abstract: Cellular totipotency is critical for whole-organism generation, yet how totipotency is established remains poorly illustrated. Abundant transposable elements (TEs) are activated in totipotent cells, which is critical for embryonic totipotency. Here, we show that the histone chaperone RBBP4, but not its homolog RBBP7, is indispensable for maintaining the identity of mouse embryonic stem cells (mESCs). Auxin-induced degradation of RBBP4, but not RBBP7, reprograms mESCs to the totipotent 2C-like cells. Also, loss of RBBP4 enhances transition from mESCs to trophoblast cells. Mechanistically, RBBP4 binds to the endogenous retroviruses (ERVs) and functions as an upstream regulator by recruiting G9a to deposit H3K9me2 on ERVL elements, and recruiting KAP1 to deposit H3K9me3 on ERV1/ERVK elements, respectively. Moreover, RBBP4 facilitates the maintenance of nucleosome occupancy at the ERVK and ERVL sites within heterochromatin regions through the chromatin remodeler CHD4. RBBP4 depletion leads to the loss of the heterochromatin marks and activation of TEs and 2C genes. Together, our findings illustrate that RBBP4 is required for heterochromatin assembly and is a critical barrier for inducing cell fate transition from pluripotency to totipotency.
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
    URL: Article
    DOI: 10.1093/nar/gkad219
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1472175-2
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    A new function of copper zinc superoxide dismutase: as a regulatory DNA-binding protein in gene expression in response to intracellular hydrogen peroxide
    Oxford University Press (OUP) ; 2019
    In:  Nucleic Acids Research Vol. 47, No. 10 ( 2019-06-04), p. 5074-5085
    Details
    In: Nucleic Acids Research, Oxford University Press (OUP), Vol. 47, No. 10 ( 2019-06-04), p. 5074-5085
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
    URL: Article
    DOI: 10.1093/nar/gkz256
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 1472175-2
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Diversified Mammalian Visual Adaptations to Bright- or Dim-Light Environments
    Oxford University Press (OUP) ; 2023
    In:  Molecular Biology and Evolution Vol. 40, No. 4 ( 2023-04-04)
    Details
    In: Molecular Biology and Evolution, Oxford University Press (OUP), Vol. 40, No. 4 ( 2023-04-04)
    Abstract: Photic niche shifts of mammals are associated with changing visual capabilities, primarily mediated by three visual pigments, two (SWS1 and M/LWS) of them for color vision and rhodopsin (RH1) for dim-light vision. To further elucidate molecular mechanisms of mammalian visual adaptations to different light environments, a systematic study incorporating evolutionary analyses across diverse groups and in vitro assays have been carried out. Here, we collected gene sequences for the three opsins from 220 species covering all major mammalian clades. After screening for cone opsin gene losses, we estimated selective pressures on each of the three genes and compared the levels of selection experienced by species living in bright- and dim-light environments. SWS1 pigment is shown to experience accelerated evolution in species living in bright-light environments as has RH1 in aquatic cetaceans, indicating potential shifts for ecological adaptations. To further elucidate the functional mechanisms for these two pigments, we then carried out site-directed mutagenesis in representative taxa. For SWS1, violet and ultraviolet sensitivities in the pika and mouse are mainly affected by substitutions at the critical sites 86 and 93, which have strong epistatic interaction. For RH1, the phenotypic difference between the sperm whale and bovine sequences is largely contributed by a substitution at site 195, which could be critical for dim-light sensation for deep-diving species. Different evolutionary patterns for the visual pigments have been identified in mammals, which correspond to photic niches, although additional phenotypic assays are still required to fully explain the functional mechanisms.
    Type of Medium: Online Resource
    ISSN: 0737-4038 , 1537-1719
    URL: Article
    DOI: 10.1093/molbev/msad063
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2024221-9
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  • 5
    Online Resource
    Online Resource
    Markhor-derived Introgression of a Genomic Region Encompassing PAPSS2 Confers High-altitude Adaptability in Tibetan Goats
    Oxford University Press (OUP) ; 2022
    In:  Molecular Biology and Evolution Vol. 39, No. 12 ( 2022-12-05)
    Details
    In: Molecular Biology and Evolution, Oxford University Press (OUP), Vol. 39, No. 12 ( 2022-12-05)
    Abstract: Understanding the genetic mechanism of how animals adapt to extreme conditions is fundamental to determine the relationship between molecular evolution and changing environments. Goat is one of the first domesticated species and has evolved rapidly to adapt to diverse environments, including harsh high-altitude conditions with low temperature and poor oxygen supply but strong ultraviolet radiation. Here, we analyzed 331 genomes of domestic goats and wild caprid species living at varying altitudes (high & gt; 3000 m above sea level and low & lt; 1200 m), along with a reference-guided chromosome-scale assembly (contig-N50: 90.4 Mb) of a female Tibetan goat genome based on PacBio HiFi long reads, to dissect the genetic determinants underlying their adaptation to harsh conditions on the Qinghai-Tibetan Plateau (QTP). Population genomic analyses combined with genome-wide association studies (GWAS) revealed a genomic region harboring the 3′-phosphoadenosine 5′-phosphosulfate synthase 2 (PAPSS2) gene showing strong association with high-altitude adaptability (PGWAS = 3.62 × 10−25) in Tibetan goats. Transcriptomic data from 13 tissues revealed that PAPSS2 was implicated in hypoxia-related pathways in Tibetan goats. We further verified potential functional role of PAPSS2 in response to hypoxia in PAPSS2-deficient cells. Introgression analyses suggested that the PAPSS2 haplotype conferring the high-altitude adaptability in Tibetan goats originated from a recent hybridization between goats and a wild caprid species, the markhor (Capra falconeri). In conclusion, our results uncover a hitherto unknown contribution of PAPSS2 to high-altitude adaptability in Tibetan goats on QTP, following interspecific introgression and natural selection.
    Type of Medium: Online Resource
    ISSN: 0737-4038 , 1537-1719
    URL: Article
    DOI: 10.1093/molbev/msac253
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2024221-9
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Identifying candidate genes and drug targets for Alzheimer’s disease by an integrative network approach using genetic and brain region-specific proteomic data
    Oxford University Press (OUP) ; 2022
    In:  Human Molecular Genetics Vol. 31, No. 19 ( 2022-09-29), p. 3341-3354
    Details
    In: Human Molecular Genetics, Oxford University Press (OUP), Vol. 31, No. 19 ( 2022-09-29), p. 3341-3354
    Abstract: Genome-wide association studies (GWAS) have identified more than 75 genetic variants associated with Alzheimer’s disease (ad). However, how these variants function and impact protein expression in brain regions remain elusive. Large-scale proteomic datasets of ad postmortem brain tissues have become available recently. In this study, we used these datasets to investigate brain region-specific molecular pathways underlying ad pathogenesis and explore their potential drug targets. We applied our new network-based tool, Edge-Weighted Dense Module Search of GWAS (EW_dmGWAS), to integrate ad GWAS statistics of 472 868 individuals with proteomic profiles from two brain regions from two large-scale ad cohorts [parahippocampal gyrus (PHG), sample size n = 190; dorsolateral prefrontal cortex (DLPFC), n = 192]. The resulting network modules were evaluated using a scale-free network index, followed by a cross-region consistency evaluation. Our EW_dmGWAS analyses prioritized 52 top module genes (TMGs) specific in PHG and 58 TMGs in DLPFC, of which four genes (CLU, PICALM, PRRC2A and NDUFS3) overlapped. Those four genes were significantly associated with ad (GWAS gene-level false discovery rate  & lt; 0.05). To explore the impact of these genetic components on TMGs, we further examined their differentially co-expressed genes at the proteomic level and compared them with investigational drug targets. We pinpointed three potential drug target genes, APP, SNCA and VCAM1, specifically in PHG. Gene set enrichment analyses of TMGs in PHG and DLPFC revealed region-specific biological processes, tissue-cell type signatures and enriched drug signatures, suggesting potential region-specific drug repurposing targets for ad.
    Type of Medium: Online Resource
    ISSN: 0964-6906 , 1460-2083
    URL: Article
    DOI: 10.1093/hmg/ddac124
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1474816-2
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    The extensin protein SAE1 plays a role in leaf senescence and is targeted by the ubiquitin ligase SINA4 in tomato
    Oxford University Press (OUP) ; 2023
    In:  Journal of Experimental Botany Vol. 74, No. 18 ( 2023-09-29), p. 5635-5652
    Details
    In: Journal of Experimental Botany, Oxford University Press (OUP), Vol. 74, No. 18 ( 2023-09-29), p. 5635-5652
    Abstract: Extensins are hydroxyproline-rich glycoproteins and generally play a structural role in cell wall integrity. In this study, we determined a novel role of tomato (Solanum lycopersicum) SENESCENCE-ASSOCIATED EXTENSIN1 (SAE1) in leaf senescence. Both gain- and loss-of-function analyses suggest that SAE1 plays a positive role in leaf senescence in tomato. Transgenic plants overexpressing SAE1 (SAE1-OX) exhibited premature leaf senescence and enhanced dark-induced senescence, whereas SAE1 knockout (SAE1-KO) plants displayed delayed development-dependent and dark-induced leaf senescence. Heterologous overexpression of SlSAE1 in Arabidopsis also led to premature leaf senescence and enhanced dark-induced senescence. In addition, the SAE1 protein was found to interact with the tomato ubiquitin ligase SlSINA4, and SlSINA4 promoted SAE1 degradation in a ligase-dependent manner when co-expressed in Nicotiana benthamiana leaves, suggesting that SlSINA4 controls SAE1 protein levels via the ubiquitin–proteasome pathway. Introduction of an SlSINA4-overexpression construct into the SAE1-OX tomato plants consistently completely eliminated accumulation of the SAE1 protein and suppressed the phenotypes conferred by overexpression of SAE1. Taken together, our results suggest that the tomato extensin SAE1 plays a positive role in leaf senescence and is regulated by the ubiquitin ligase SINA4.
    Type of Medium: Online Resource
    ISSN: 0022-0957 , 1460-2431
    URL: Article
    DOI: 10.1093/jxb/erad242
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1466717-4
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    CSEA-DB: an omnibus for human complex trait and cell type associations
    Oxford University Press (OUP) ; 2021
    In:  Nucleic Acids Research Vol. 49, No. D1 ( 2021-01-08), p. D862-D870
    Details
    In: Nucleic Acids Research, Oxford University Press (OUP), Vol. 49, No. D1 ( 2021-01-08), p. D862-D870
    Abstract: During the past decade, genome-wide association studies (GWAS) have identified many genetic variants with susceptibility to several thousands of complex diseases or traits. The genetic regulation of gene expression is highly tissue-specific and cell type-specific. Recently, single-cell technology has paved the way to dissect cellular heterogeneity in human tissues. Here, we present a reference database for GWAS trait-associated cell type-specificity, named Cell type-Specific Enrichment Analysis DataBase (CSEA-DB, available at https://bioinfo.uth.edu/CSEADB/). Specifically, we curated total of 5120 GWAS summary statistics data for a wide range of human traits and diseases followed by rigorous quality control. We further collected & gt;900 000 cells from the leading consortia such as Human Cell Landscape, Human Cell Atlas, and extensive literature mining, including 752 tissue cell types from 71 adult and fetal tissues across 11 human organ systems. The tissues and cell types were annotated with Uberon and Cell Ontology. By applying our deTS algorithm, we conducted 10 250 480 times of trait-cell type associations, reporting a total of 598 (11.68%) GWAS traits with at least one significantly associated cell type. In summary, CSEA-DB could serve as a repository of association map for human complex traits and their underlying cell types, manually curated GWAS, and single-cell transcriptome resources.
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
    URL: Article
    DOI: 10.1093/nar/gkaa1064
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1472175-2
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    YY1 safeguard multidimensional epigenetic landscape associated with extended pluripotency
    Oxford University Press (OUP) ; 2022
    In:  Nucleic Acids Research Vol. 50, No. 21 ( 2022-11-28), p. 12019-12038
    Details
    In: Nucleic Acids Research, Oxford University Press (OUP), Vol. 50, No. 21 ( 2022-11-28), p. 12019-12038
    Abstract: Although extended pluripotent stem cells (EPSCs) have the potential to form both embryonic and extraembryonic lineages, how their transcriptional regulatory mechanism differs from that of embryonic stem cells (ESCs) remains unclear. Here, we discovered that YY1 binds to specific open chromatin regions in EPSCs. Yy1 depletion in EPSCs leads to a gene expression pattern more similar to that of ESCs than control EPSCs. Moreover, Yy1 depletion triggers a series of epigenetic crosstalk activities, including changes in DNA methylation, histone modifications and high-order chromatin structures. Yy1 depletion in EPSCs disrupts the enhancer-promoter (EP) interactions of EPSC-specific genes, including Dnmt3l. Yy1 loss results in DNA hypomethylation and dramatically reduces the enrichment of H3K4me3 and H3K27ac on the promoters of EPSC-specific genes by upregulating the expression of Kdm5c and Hdac6 through facilitating the formation of CCCTC-binding factor (CTCF)-mediated EP interactions surrounding their loci. Furthermore, single-cell RNA sequencing (scRNA-seq) experiments revealed that YY1 is required for the derivation of extraembryonic endoderm (XEN)-like cells from EPSCs in vitro. Together, this study reveals that YY1 functions as a key regulator of multidimensional epigenetic crosstalk associated with extended pluripotency.
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
    URL: Article
    DOI: 10.1093/nar/gkac230
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1472175-2
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    Diverse Roles of the Salicylic Acid Receptors NPR1 and NPR3/NPR4 in Plant Immunity
    Oxford University Press (OUP) ; 2020
    In:  The Plant Cell Vol. 32, No. 12 ( 2020-12), p. 4002-4016
    Details
    In: The Plant Cell, Oxford University Press (OUP), Vol. 32, No. 12 ( 2020-12), p. 4002-4016
    Type of Medium: Online Resource
    ISSN: 1040-4651 , 1532-298X
    URL: Article
    DOI: 10.1105/tpc.20.00499
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 623171-8
    detail.hit.zdb_id: 2004373-9
    SSG: 12
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