Abstract:
:Despite the well-documented role of remote enhancers in controlling developmental gene expression, the mechanisms that allocate enhancers to genes are poorly characterized. Here, we investigate the cis-regulatory organization of the locus containing the Tfap2c and Bmp7 genes in vivo, using a series of engineered chromosomal rearrangements. While these genes lie adjacent to one another, we demonstrate that they are independently regulated by distinct sets of enhancers, which in turn define non-overlapping regulatory domains. Chromosome conformation capture experiments reveal a corresponding partition of the locus in two distinct structural entities, demarcated by a discrete transition zone. The impact of engineered chromosomal rearrangements on the topology of the locus and the resultant gene expression changes indicate that this transition zone functionally organizes the structural partition of the locus, thereby defining enhancer-target gene allocation. This partition is, however, not absolute: we show that it allows competing interactions across it that may be non-productive for the competing gene, but modulate expression of the competed one. Altogether, these data highlight the prime role of the topological organization of the genome in long-distance regulation of gene expression.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Tsujimura T,Klein FA,Langenfeld K,Glaser J,Huber W,Spitz Fdoi
10.1371/journal.pgen.1004897subject
Has Abstractpub_date
2015-01-08 00:00:00pages
e1004897issue
1eissn
1553-7390issn
1553-7404pii
PGENETICS-D-14-02222journal_volume
11pub_type
杂志文章相关文献
PLoS Genetics文献大全abstract::Phosphorylated Spo0A is a master regulator of stationary phase development in the model bacterium Bacillus subtilis, controlling the formation of spores, biofilms, and cells competent for transformation. We have monitored the rate of transcription of the spo0A gene during growth in sporulation medium using promoter fu...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002048
更新日期:2011-04-01 00:00:00
abstract::Determining how facultative anaerobic organisms sense and direct cellular responses to electron acceptor availability has been a subject of intense study. However, even in the model organism Escherichia coli, established mechanisms only explain a small fraction of the hundreds of genes that are regulated during electr...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004264
更新日期:2014-04-03 00:00:00
abstract::Formation of elaborately branched dendrites is necessary for the proper input and connectivity of many sensory neurons. Previous studies have revealed that dendritic growth relies heavily on ER-to-Golgi transport, Golgi outposts and endocytic recycling. How new membrane and associated cargo is delivered from the secre...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005484
更新日期:2015-09-22 00:00:00
abstract::Methylcytosine-binding proteins decipher the epigenetic information encoded by DNA methylation and provide a link between DNA methylation, modification of chromatin structure, and gene silencing. VARIANT IN METHYLATION 1 (VIM1) encodes an SRA (SET- and RING-associated) domain methylcytosine-binding protein in Arabidop...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000156
更新日期:2008-08-15 00:00:00
abstract::All living organisms exist in a precarious state of homeostasis that requires constant maintenance. A wide variety of stresses, including hypoxia, heat, and infection by pathogens perpetually threaten to imbalance this state. Organisms use a battery of defenses to mitigate damage and restore normal function. Previousl...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006876
更新日期:2017-06-29 00:00:00
abstract::ATP-dependent chromatin remodelers control DNA access for transcription, recombination, and other processes. Acf1 (also known as BAZ1A in mammals) is a defining subunit of the conserved ISWI-family chromatin remodelers ACF and CHRAC, first purified over 15 years ago from Drosophila melanogaster embryos. Much is known ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003945
更新日期:2013-11-01 00:00:00
abstract::Chronic inflammation promotes oncogenic transformation and tumor progression. Many inflammatory agents also generate a toxic microenvironment, implying that adaptive mechanisms must be deployed for cells to survive and undergo transformation in such unfavorable contexts. A paradigmatic case is represented by cancers o...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007380
更新日期:2018-05-07 00:00:00
abstract::We report association mapping of a locus on bovine chromosome 3 that underlies a Mendelian form of stunted growth in Belgian Blue Cattle (BBC). By resequencing positional candidates, we identify the causative c124-2A>G splice variant in intron 1 of the RNF11 gene, for which all affected animals are homozygous. We make...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002581
更新日期:2012-01-01 00:00:00
abstract::Pervasive natural selection can strongly influence observed patterns of genetic variation, but these effects remain poorly understood when multiple selected variants segregate in nearby regions of the genome. Classical population genetics fails to account for interference between linked mutations, which grows increasi...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004222
更新日期:2014-03-27 00:00:00
abstract::With multiple genome-wide association studies (GWAS) performed across autoimmune diseases, there is a great opportunity to study the homogeneity of genetic architectures across autoimmune disease. Previous approaches have been limited in the scope of their analysis and have failed to properly incorporate the direction...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000792
更新日期:2009-12-01 00:00:00
abstract::Accurate methods to assess the pathogenicity of mutations are needed to fully leverage the possibilities of genome sequencing in diagnosis. Current data-driven and bioinformatics approaches are, however, limited by the large number of new variations found in each newly sequenced genome, and often do not provide direct...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006739
更新日期:2017-04-19 00:00:00
abstract::Almost 60 years ago, Severo Ochoa was awarded the Nobel Prize in Physiology or Medicine for his discovery of the enzymatic synthesis of RNA by polynucleotide phosphorylase (PNPase). Although this discovery provided an important tool for deciphering the genetic code, subsequent work revealed that the predominant functi...
journal_title:PLoS genetics
pub_type: 杂志文章,评审
doi:10.1371/journal.pgen.1007654
更新日期:2018-10-11 00:00:00
abstract::The Cleavage Factor 1A (CF1A) complex, which is required for the termination of transcription in budding yeast, occupies the 3' end of transcriptionally active genes. We recently demonstrated that CF1A subunits also crosslink to the 5' end of genes during transcription. The presence of CF1A complex at the promoter sug...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003722
更新日期:2013-01-01 00:00:00
abstract::The evolution of insecticide resistance is a global constraint to agricultural production. Spinosad is a new, low-environmental-risk insecticide that primarily targets nicotinic acetylcholine receptors (nAChR) and is effective against a wide range of pest species. However, after only a few years of application, field ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000802
更新日期:2010-01-01 00:00:00
abstract::Candida albicans is a normal resident of the gastrointestinal tract and also the most prevalent fungal pathogen of humans. It last shared a common ancestor with the model yeast Saccharomyces cerevisiae over 300 million years ago. We describe a collection of 143 genetically matched strains of C. albicans, each of which...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000783
更新日期:2009-12-01 00:00:00
abstract::Intraflagellar transport (IFT) particles or trains are composed of IFT-A and IFT-B complexes. To assess the working mechanism of the IFT-A complex in IFT and ciliogenesis, we have analyzed ift43 mutants of Chlamydomnonas in conjunction with mutants of the other IFT-A subunits. An ift43 null mutant or a mutant with a p...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006627
更新日期:2017-02-16 00:00:00
abstract::Deedu (DU) Mongolians, who migrated from the Mongolian steppes to the Qinghai-Tibetan Plateau approximately 500 years ago, are challenged by environmental conditions similar to native Tibetan highlanders. Identification of adaptive genetic factors in this population could provide insight into coordinated physiological...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003634
更新日期:2013-01-01 00:00:00
abstract::The genetics of lymphoma susceptibility reflect the marked heterogeneity of diseases that comprise this broad phenotype. However, multiple subtypes of lymphoma are observed in some families, suggesting shared pathways of genetic predisposition to these pathologically distinct entities. Using a two-stage GWAS, we teste...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003220
更新日期:2013-01-01 00:00:00
abstract::The neural crest (NC) is a vertebrate-specific cell population that exhibits remarkable multipotency. Although derived from the neural plate border (NPB) ectoderm, cranial NC (CNC) cells contribute not only to the peripheral nervous system but also to the ectomesenchymal precursors of the head skeleton. To date, the d...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002938
更新日期:2012-09-01 00:00:00
abstract::Gene conversion, the non-reciprocal exchange of genetic information, is one of the potential products of meiotic recombination. It can shape genome structure by acting on repetitive DNA elements, influence allele frequencies at the population level, and is known to be implicated in human disease. But gene conversion i...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002968
更新日期:2012-01-01 00:00:00
abstract::The exclusive localization of the histone H3 variant CENP-A to centromeres is essential for accurate chromosome segregation. Ubiquitin-mediated proteolysis helps to ensure that CENP-A does not mislocalize to euchromatin, which can lead to genomic instability. Consistent with this, overexpression of the budding yeast C...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005930
更新日期:2016-03-16 00:00:00
abstract::During pancreatic development, transcription factor cascades gradually commit precursor populations to the different endocrine cell fate pathways. Although mutational analyses have defined the functions of many individual pancreatic transcription factors, the integrative transcription factor networks required to regul...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003278
更新日期:2013-01-01 00:00:00
abstract::The clinical spectrum of ciliopathies affecting motile cilia spans impaired mucociliary clearance in the respiratory system, laterality defects including heart malformations, infertility and hydrocephalus. Using linkage analysis and whole exome sequencing, we identified two recessive loss-of-function MNS1 mutations in...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007602
更新日期:2018-08-27 00:00:00
abstract::Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic...
journal_title:PLoS genetics
pub_type: 杂志文章,meta分析
doi:10.1371/journal.pgen.1007813
更新日期:2018-12-19 00:00:00
abstract::The Core Binding Factor (CBF) protein RUNX1 is a master regulator of definitive hematopoiesis, crucial for hematopoietic stem cell (HSC) emergence during ontogeny. RUNX1 also plays vital roles in adult mice, in regulating the correct specification of numerous blood lineages. Akin to the other mammalian Runx genes, Run...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005814
更新日期:2016-01-25 00:00:00
abstract::X-linked myotubular myopathy (XLMTM) is a congenital disorder caused by mutations of the myotubularin gene, MTM1. Myotubularin belongs to a large family of conserved lipid phosphatases that include both catalytically active and inactive myotubularin-related proteins (i.e., "MTMRs"). Biochemically, catalytically inacti...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003583
更新日期:2013-06-01 00:00:00
abstract::Bacteria can arrest their own growth and proliferation upon nutrient depletion and under various stressful conditions to ensure their survival. However, the molecular mechanisms responsible for suppressing growth and arresting the cell cycle under such conditions remain incompletely understood. Here, we identify post-...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005342
更新日期:2015-07-02 00:00:00
abstract::Polycomb (PcG) regulation has been thought to produce stable long-term gene silencing. Genomic analyses in Drosophila and mammals, however, have shown that it targets many genes, which can switch state during development. Genetic evidence indicates that critical for the active state of PcG target genes are the histone...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000805
更新日期:2010-01-01 00:00:00
abstract::We propose a novel statistical framework for integrating the result from molecular quantitative trait loci (QTL) mapping into genome-wide genetic association analysis of complex traits, with the primary objectives of quantitatively assessing the enrichment of the molecular QTLs in complex trait-associated genetic vari...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006646
更新日期:2017-03-09 00:00:00
abstract::Despite strong vetting for disease activity, only 10% of candidate new molecular entities in early stage clinical trials are eventually approved. Analyzing historical pipeline data, Nelson et al. 2015 (Nat. Genet.) concluded pipeline drug targets with human genetic evidence of disease association are twice as likely t...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008489
更新日期:2019-12-12 00:00:00