Abstract:
BACKGROUND:Genome-scale pooled CRISPR screens are powerful tools for identifying genetic dependencies across varied cellular processes. The vast majority of CRISPR screens reported to date have focused exclusively on the perturbation of protein-coding gene function. However, protein-coding genes comprise < 2% of the sequence space in the human genome leaving a substantial portion of the genome uninterrogated. Noncoding regions of the genome harbor important regulatory elements (e.g. promoters, enhancers, silencers) that influence cellular processes but high-throughput methods for evaluating their essentiality have yet to be established. RESULTS:Here, we describe a CRISPR-based screening approach that facilitates the functional profiling of thousands of noncoding regulatory elements in parallel. We selected the tumor suppressor p53 as a model system and designed a pooled CRISPR library targeting thousands of p53 binding sites throughout the genome. Following transduction into dCas9-KRAB-expressing cells we identified several regulatory elements that influence cell proliferation. Moreover, we uncovered multiple elements that are required for the p53-mediated DNA damage response. Surprisingly, many of these elements are located deep within intergenic regions of the genome that have no prior functional annotations. CONCLUSIONS:This work diversifies the applications for pooled CRISPR screens and provides a framework for future functional studies focused on noncoding regulatory elements.
journal_name
BMC Genomicsjournal_title
BMC genomicsauthors
Borys SM,Younger STdoi
10.1186/s12864-020-6497-0subject
Has Abstractpub_date
2020-01-31 00:00:00pages
107issue
1issn
1471-2164pii
10.1186/s12864-020-6497-0journal_volume
21pub_type
杂志文章相关文献
BMC GENOMICS文献大全abstract:BACKGROUND:While increasing data on bacterial evolution in controlled environments are available, our understanding of bacterial genome evolution in natural environments is limited. We thus performed full genome analyses on four Listeria monocytogenes, including human and food isolates from both a 1988 case of sporadic...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-9-539
更新日期:2008-11-13 00:00:00
abstract:BACKGROUND:Lychas mucronatus is one scorpion species widely distributed in Southeast Asia and southern China. Anything is hardly known about its venom components, despite the fact that it can often cause human accidents. In this work, we performed a venomous gland transcriptome analysis by constructing and screening th...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-11-452
更新日期:2010-07-28 00:00:00
abstract:BACKGROUND:Lipopolysaccharide (LPS) endotoxin stimulates pro-inflammatory pathways and is a key player in the pathological mechanisms involved in the development of endometritis. This study aimed to investigate LPS-induced DNA methylation changes in bovine endometrial epithelial cells (bEECs), which may affect endometr...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-020-06777-7
更新日期:2020-06-03 00:00:00
abstract:BACKGROUND:It has been shown previously that aminocoumarin antibiotics such as novobiocin lead to immediate downregulation of recA expression and thereby inhibit the SOS response, mutation frequency and recombination capacity in Staphylococcus aureus. Aminocoumarins function by inhibiting the ATPase activity of DNA gyr...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-15-291
更新日期:2014-04-16 00:00:00
abstract:BACKGROUND:Bacterial genomes possess varying GC content (total guanines (Gs) and cytosines (Cs) per total of the four bases within the genome) but within a given genome, GC content can vary locally along the chromosome, with some regions significantly more or less GC rich than on average. We have examined how the GC co...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-11-464
更新日期:2010-08-06 00:00:00
abstract:BACKGROUND:Whilst being closely related to the model actinomycete Streptomyces coelicolor A3(2), S. lividans 66 differs from it in several significant and phenotypically observable ways, including antibiotic production. Previous comparative gene hybridization studies investigating such differences have used low-density...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-11-682
更新日期:2010-12-01 00:00:00
abstract:BACKGROUND:Miniature inverted repeat transposable element (MITE) is one type of transposable element (TE), which is largely found in eukaryotic genomes and involved in a wide variety of biological events. However, only few MITEs were proved to be currently active and their physiological function remains largely unknown...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-13-135
更新日期:2012-04-13 00:00:00
abstract:BACKGROUND:Haplotypes combine the effects of several single nucleotide polymorphisms (SNPs) with high linkage disequilibrium, which benefit the genome-wide association analysis (GWAS). In the haplotype association analysis, both haplotype alleles and blocks are tested. Haplotype alleles can be inferred with the same st...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-020-6552-x
更新日期:2020-02-11 00:00:00
abstract:BACKGROUND:Pectins are plant cell wall polysaccharides that can be acetylated on C2 and/or C3 of galacturonic acid residues. The degree of acetylation of pectin can be modulated by pectin acetylesterase (EC 3.1.1.6, PAE). The function and structure of plant PAEs remain poorly understood and the role of the fine-tuning ...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-017-3833-0
更新日期:2017-06-08 00:00:00
abstract:BACKGROUND:Thousands of intragenic long interspersed element 1 sequences (LINE-1 elements or L1s) reside within genes. These intragenic L1 sequences are conserved and regulate the expression of their host genes. When L1 methylation is decreased, either through chemical induction or in cancer, the intragenic L1 transcri...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-14-205
更新日期:2013-03-27 00:00:00
abstract:BACKGROUND:Copy number variants (CNVs) have been shown to increase risk for physical anomalies, developmental, psychiatric and medical disorders. Some of them have been associated with changes in weight, height, and other physical traits. As most studies have been performed on children and young people, these effects o...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-018-5292-7
更新日期:2018-12-04 00:00:00
abstract:BACKGROUND:Quantitative trait locus (QTL) studies show that variation in salinity tolerance in Arctic charr and rainbow trout has a genetic basis, even though both these species have low to moderate salinity tolerance capacities. QTL were observed to localize to homologous linkage group segments within putative chromos...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-13-420
更新日期:2012-08-24 00:00:00
abstract:BACKGROUND:The recent advances in next generation sequencing technology have made the sequencing of RNA (i.e., RNA-Seq) an extemely popular approach for gene expression analysis. Identification of significant differential expression represents a crucial initial step in these analyses, on which most subsequent inference...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-016-2848-2
更新日期:2016-08-04 00:00:00
abstract:BACKGROUND:Acquisition of external phosphorus (P) and optimisation of internal P are essential for plant growth and development, and insufficient availability of P in soils is a major challenge in agriculture. Members of the purple acid phosphatase (PAP) family of enzymes are candidates for increasing P use efficiency....
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-018-5022-1
更新日期:2018-08-31 00:00:00
abstract:BACKGROUND:Small bioinformatics databases, unlike institutionally funded large databases, are vulnerable to discontinuation and many reported in publications are no longer accessible. This leads to irreproducible scientific work and redundant effort, impeding the pace of scientific progress. RESULTS:We describe a Web-...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-14-S5-S13
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Campylobacter is the leading cause of foodborne diarrhoeal illness in humans and is mostly acquired from consumption or handling of contaminated poultry meat. In the absence of effective licensed vaccines and inhibitors, selection for chickens with increased resistance to Campylobacter could potentially redu...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-016-2612-7
更新日期:2016-04-18 00:00:00
abstract:BACKGROUND:Gene duplication underlies a significant proportion of gene functional diversity and genome complexity in both eukaryotes and prokaryotes. Although several reports in the literature described the duplication of specific genes in E. coli, a detailed analysis of the extent of gene duplications in this microorg...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-019-5683-4
更新日期:2019-04-24 00:00:00
abstract:BACKGROUND:Improving fiber quality is a major challenge in cotton breeding, since the molecular basis of fiber quality traits is poorly understood. Fine mapping and candidate gene prediction of quantitative trait loci (QTL) controlling cotton fiber quality traits can help to elucidate the molecular basis of fiber quali...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-016-2605-6
更新日期:2016-04-19 00:00:00
abstract:BACKGROUND:Sequencing data from The Cancer Genome Atlas (TGCA), the International Cancer Genome Consortium and other research institutes have revealed the presence of genetic alterations in several tumor types, including gastric cancer. These data have been combined into a catalog of significantly mutated genes for eac...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-016-3166-4
更新日期:2016-10-26 00:00:00
abstract:BACKGROUND:To develop evolutionary models for the free living bacterium Alteromonas the genome sequences of isolates of the genus have been extensively analyzed. However, the main genetic exchange drivers in these microbes, conjugative elements (CEs), have not been considered in detail thus far. In this work, CEs have ...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-016-3461-0
更新日期:2017-01-05 00:00:00
abstract:BACKGROUND:Adjuvant Radiotherapy (RT) after surgical removal of tumors proved beneficial in long-term tumor control and treatment planning. For many years, it has been well concluded that radio-sensitivities of tumors upon radiotherapy decrease according to the sizes of tumors and RT models based on Poisson statistics ...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-9-S2-S9
更新日期:2008-09-16 00:00:00
abstract:BACKGROUND:Identification and classification of highly similar microbial strains is a challenging issue in microbiology, ecology and evolutionary biology. Among various available approaches, gene content analysis is also at the core of microbial taxonomy. However, no threshold has been determined for grouping microorgn...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-016-2991-9
更新日期:2016-08-17 00:00:00
abstract:BACKGROUND:Rich in genetic information and cost-effective to genotype, the Insertion-Deletion (InDel) molecular marker system is an important tool for studies in genetics, genomics and for marker-assisted breeding. Advent of next-generation sequencing (NGS) revolutionized the speed and throughput of sequence data gener...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-016-2614-5
更新日期:2016-04-14 00:00:00
abstract:BACKGROUND:In most species of mammals, the TRB locus has the common feature of a library of TRBV genes positioned at the 5'- end of two in tandem aligned D-J-C gene clusters, each composed of a single TRBD gene, 6-7 TRBJ genes and one TRBC gene. An enhancer located at the 3'end of the last TRBC and a well-defined promo...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-11-3
更新日期:2010-01-04 00:00:00
abstract:BACKGROUND:Limited nutrient availability during development is associated with metabolic diseases in adulthood. The molecular cause for these defects is unclear. Here, we investigate if transcriptional changes caused by developmental malnutrition reveal an early response that can be linked to metabolism and metabolic d...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-015-1654-6
更新日期:2015-06-04 00:00:00
abstract:BACKGROUND:Transposable Elements (TEs) are key components that shape the organization and evolution of genomes. Fungi have developed defense mechanisms against TE invasion such as RIP (Repeat-Induced Point mutation), MIP (Methylation Induced Premeiotically) and Quelling (RNA interference). RIP inactivates repeated sequ...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-015-1347-1
更新日期:2015-02-28 00:00:00
abstract:BACKGROUND:Single nucleotide polymorphisms (SNPs) and insertions/deletions (InDels) are the major genetic variations and are distributed extensively across the whole plant genome. However, few studies of these variations have been conducted in the long-lived perennial tea plant. RESULTS:In this study, we investigated ...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-019-6347-0
更新日期:2019-12-05 00:00:00
abstract:BACKGROUND:The plastome of medicinal and endangered species in Kingdom of Saudi Arabia, Barleria prionitis was sequenced. The plastome was compared with that of seven Acanthoideae species in order to describe the plastome, spot the microsatellite, assess the dissimilarities within the sampled plastomes and to infer the...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-020-06798-2
更新日期:2020-06-06 00:00:00
abstract:BACKGROUND:Improvements in poultry production within the past 50 years have led to increased muscle yield and growth rate, which may be contributing to an increased rate and development of new muscle disorders in chickens. Previously reported muscle disorders and conditions are generally associated with poor meat quali...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-015-1623-0
更新日期:2015-05-21 00:00:00
abstract:BACKGROUND:Phlebotomine sand flies (Diptera, Nematocera) are important vectors of several pathogens, including Leishmania parasites, causing serious diseases of humans and dogs. Despite their importance as disease vectors, most aspects of sand fly biology remain unknown including the molecular basis of their reproducti...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-019-5898-4
更新日期:2019-06-25 00:00:00