Abstract:
:Cis-regulation plays an essential role in the control of gene expression, and is particularly complex and poorly understood for developmental genes, which are subject to multiple levels of modulation. In this study, we performed a global analysis of the cis-acting elements involved in the control of the zebrafish developmental gene krox20. krox20 encodes a transcription factor required for hindbrain segmentation and patterning, a morphogenetic process highly conserved during vertebrate evolution. Chromatin accessibility analysis reveals a cis-regulatory landscape that includes 6 elements participating in the control of initiation and autoregulatory aspects of krox20 hindbrain expression. Combining transgenic reporter analyses and CRISPR/Cas9-mediated mutagenesis, we assign precise functions to each of these 6 elements and provide a comprehensive view of krox20 cis-regulation. Three important features emerged. First, cooperation between multiple cis-elements plays a major role in the regulation. Cooperation can surprisingly combine synergy and redundancy, and is not restricted to transcriptional enhancer activity (for example, 4 distinct elements cooperate through different modes to maintain autoregulation). Second, several elements are unexpectedly versatile, which allows them to be involved in different aspects of control of gene expression. Third, comparative analysis of the elements and their activities in several vertebrate species reveals that this versatility is underlain by major plasticity across evolution, despite the high conservation of the gene expression pattern. These characteristics are likely to be of broad significance for developmental genes.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Torbey P,Thierion E,Collombet S,de Cian A,Desmarquet-Trin-Dinh C,Dura M,Concordet JP,Charnay P,Gilardi-Hebenstreit Pdoi
10.1371/journal.pgen.1007581subject
Has Abstractpub_date
2018-08-06 00:00:00pages
e1007581issue
8eissn
1553-7390issn
1553-7404pii
PGENETICS-D-18-01068journal_volume
14pub_type
杂志文章相关文献
PLoS Genetics文献大全abstract::Transcription factors are grouped into families based on sequence similarity within functional domains, particularly DNA-binding domains. The Specificity proteins Sp1, Sp2 and Sp3 are paradigmatic of closely related transcription factors. They share amino-terminal glutamine-rich regions and a conserved carboxy-termina...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005102
更新日期:2015-03-20 00:00:00
abstract::Communication between neoplastic cells and cells of their microenvironment is critical to cancer progression. To investigate the role of cytoneme-mediated signaling as a mechanism for distributing growth factor signaling proteins between tumor and tumor-associated cells, we analyzed EGFR and RET Drosophila tumor model...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008415
更新日期:2019-09-30 00:00:00
abstract::The oligodendrocyte density is greater and myelin sheaths are thicker in the adult male mouse brain when compared with females. Here, we show that these sex differences emerge during the first 10 postnatal days, precisely at a stage when a late wave of oligodendrocyte progenitor cells arises and starts differentiating...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007049
更新日期:2017-11-06 00:00:00
abstract::The Ku complex binds non-specifically to DNA breaks and ensures repair via NHEJ. However, Ku is also known to bind directly to telomeric DNA ends and its presence there is associated with telomere capping, but avoiding NHEJ. How the complex discriminates between a DNA break and a telomeric extremity remains unknown. O...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006479
更新日期:2016-12-08 00:00:00
abstract::The integration of expression profiling with linkage analysis has increasingly been used to identify genes underlying complex phenotypes. The effects of gender on the regulation of many physiological traits are well documented; however, "genetical genomic" analyses have not yet addressed the degree to which their conc...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0020015
更新日期:2006-02-01 00:00:00
abstract::Fragile X syndrome, a common form of inherited mental retardation, is caused by the loss of fragile X mental retardation protein (FMRP). We have previously demonstrated that dFmr1, the Drosophila ortholog of the fragile X mental retardation 1 gene, plays a role in the proper maintenance of germline stem cells in Droso...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000444
更新日期:2009-04-01 00:00:00
abstract::Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant muscular dystrophy in which no mutation of pathogenic gene(s) has been identified. Instead, the disease is, in most cases, genetically linked to a contraction in the number of 3.3 kb D4Z4 repeats on chromosome 4q. How contraction of the 4qter D4Z4 repeats c...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000559
更新日期:2009-07-01 00:00:00
abstract::Domestic dog breeds exhibit remarkable morphological variations that result from centuries of artificial selection and breeding. Identifying the genetic changes that contribute to these variations could provide critical insights into the molecular basis of tissue and organismal morphogenesis. Bulldogs, French Bulldogs...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007850
更新日期:2018-12-06 00:00:00
abstract::Mimulus guttatus and M. nasutus are an evolutionary and ecological model sister species pair differentiated by ecology, mating system, and partial reproductive isolation. Despite extensive research on this system, the history of divergence and differentiation in this sister pair is unclear. We present and analyze a po...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004410
更新日期:2014-06-26 00:00:00
abstract::The modification of transcriptional regulation has become increasingly appreciated as a major contributor to morphological evolution. However, the role of negative-acting control elements (e.g. silencers) in generating morphological diversity has been generally overlooked relative to positive-acting "enhancer" element...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005279
更新日期:2015-06-26 00:00:00
abstract::Adult skeletal muscles are maintained during homeostasis and regenerated upon injury by muscle stem cells (MuSCs). A heterogeneity in self-renewal, differentiation and regeneration properties has been reported for MuSCs based on their anatomical location. Although MuSCs derived from extraocular muscles (EOM) have a hi...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1009022
更新日期:2020-10-30 00:00:00
abstract::In response to stress and injury a coordinated activation of conserved signalling modules, such as JNK and JAK/STAT, is critical to trigger regenerative tissue restoration. While these pathways rebuild homeostasis and promote faithful organ recovery, it is intriguing that they also become activated in various tumour c...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007187
更新日期:2018-01-22 00:00:00
abstract::New systems genetics approaches are needed to rapidly identify host genes and genetic networks that regulate complex disease outcomes. Using genetically diverse animals from incipient lines of the Collaborative Cross mouse panel, we demonstrate a greatly expanded range of phenotypes relative to classical mouse models ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005504
更新日期:2015-10-09 00:00:00
abstract::MicroRNAs (miRNAs) play important roles in normal cellular differentiation and oncogenesis. microRNA93 (mir-93), a member of the mir106b-25 cluster, located in intron 13 of the MCM7 gene, although frequently overexpressed in human malignancies may also function as a tumor suppressor gene. Using a series of breast canc...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002751
更新日期:2012-01-01 00:00:00
abstract::Recent studies of the HapMap lymphoblastoid cell lines have identified large numbers of quantitative trait loci for gene expression (eQTLs). Reanalyzing these data using a novel Bayesian hierarchical model, we were able to create a surprisingly high-resolution map of the typical locations of sites that affect mRNA lev...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000214
更新日期:2008-10-01 00:00:00
abstract::A cascade of alternative sigma factors directs developmental gene expression during spore formation by the bacterium Bacillus subtilis. As the spore develops, a tightly regulated switch occurs in which the early-acting sigma factor σF is replaced by the late-acting sigma factor σG. The gene encoding σG (sigG) is trans...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007350
更新日期:2018-04-27 00:00:00
abstract::Spatial arrangement of neurite branching is instructed by both attractive and repulsive cues. Here we show that in C. elegans, the Wnt family of secreted glycoproteins specify neurite branching sites in the PLM mechanosensory neurons. Wnts function through MIG-1/Frizzled and the planar cell polarity protein (PCP) VANG...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006720
更新日期:2017-04-06 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pgen.1000832.]. ...
journal_title:PLoS genetics
pub_type: 杂志文章,已发布勘误
doi:10.1371/journal.pgen.1007392
更新日期:2018-05-16 00:00:00
abstract::Human FTO gene variants are associated with body mass index and type 2 diabetes. Because the obesity-associated SNPs are intronic, it is unclear whether changes in FTO expression or splicing are the cause of obesity or if regulatory elements within intron 1 influence upstream or downstream genes. We tested the idea th...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000599
更新日期:2009-08-01 00:00:00
abstract::From genomic association studies, quantitative trait loci analysis, and epigenomic mapping, it is evident that significant efforts are necessary to define genetic-epigenetic interactions and understand their role in disease susceptibility and progression. For this reason, an analysis of the effects of genetic variatio...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007785
更新日期:2018-11-19 00:00:00
abstract::Phenotypic variation within an isogenic bacterial population is thought to ensure the survival of a subset of cells in adverse conditions. The opportunistic pathogen Pseudomonas aeruginosa variably expresses several phenotypes, including antibiotic resistance, biofilm formation, and the production of CupA fimbriae. He...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000779
更新日期:2009-12-01 00:00:00
abstract::The contribution of MEF2 TFs to the tumorigenic process is still mysterious. Here we clarify that MEF2 can support both pro-oncogenic or tumor suppressive activities depending on the interaction with co-activators or co-repressors partners. Through these interactions MEF2 supervise histone modifications associated wit...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006752
更新日期:2017-04-18 00:00:00
abstract::Complete metamorphosis (Holometaboly) is a key innovation that underlies the spectacular success of holometabolous insects. Phylogenetic analyses indicate that Holometabola form a monophyletic group that evolved from ancestors exhibiting hemimetabolous development (Hemimetaboly). However, the nature of the changes und...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006020
更新日期:2016-05-02 00:00:00
abstract::We recently reported that centrosomal protein 164 (CEP164) regulates both cilia and the DNA damage response in the autosomal recessive polycystic kidney disease nephronophthisis. Here we examine the functional role of CEP164 in nephronophthisis-related ciliopathies and concomitant fibrosis. Live cell imaging of RPE-FU...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004594
更新日期:2014-10-23 00:00:00
abstract::Multiple endocrine neoplasia type 2B (MEN2B) is a highly aggressive thyroid cancer syndrome. Since almost all sporadic cases are caused by the same nucleotide substitution in the RET proto-oncogene, the calculated disease incidence is 100-200 times greater than would be expected based on the genome average mutation fr...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002420
更新日期:2012-01-01 00:00:00
abstract::Autosomal recessive congenital ichthyosis (ARCI) is a rare genetic disorder of the skin characterized by abnormal desquamation over the whole body. In this study we report four patients from three consanguineous Tunisian families with skin, eye, heart, and skeletal anomalies, who harbor a homozygous contiguous gene de...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003536
更新日期:2013-06-01 00:00:00
abstract::Polygenic scores are increasingly powerful predictors of educational achievement. It is unclear, however, how sets of polygenic scores, which partly capture environmental effects, perform jointly with sets of environmental measures, which are themselves heritable, in prediction models of educational achievement. Here,...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1009153
更新日期:2020-11-17 00:00:00
abstract::Seam cells in Caenorhabditis elegans provide a paradigm for the stem cell mode of division, with the ability to both self-renew and produce daughters that differentiate. The transcription factor RNT-1 and its DNA binding partner BRO-1 (homologues of the mammalian cancer-associated stem cell regulators RUNX and CBFβ, r...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002200
更新日期:2011-08-01 00:00:00
abstract::miRNAs are small RNAs directing many developmental processes by posttranscriptional regulation of protein-coding genes. We uncovered a new role for miR-1-1/133a-2 and miR-1-2/133a-1 clusters in the specification of embryonic cardiomyocytes allowing transition from an immature state characterized by expression of smoot...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003793
更新日期:2013-01-01 00:00:00
abstract::Understanding buffering mechanisms for various perturbations is essential for understanding robustness in cellular systems. Protein-level dosage compensation, which arises when changes in gene copy number do not translate linearly into protein level, is one mechanism for buffering against genetic perturbations. Here, ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006554
更新日期:2017-01-25 00:00:00