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Autor:Raines AM; Magella B; Adam M; Potter SSEndere?o:Division of Developmental Biology, Cincinnati Children's Medical Center, 3333 Burnet Ave., Cincinnati, OH, 45229, USA. ....
Título:Key pathways regulated by HoxA9,10,11/HoxD9,10,11 during limb development.
Fonte:BMC Dev B 15:28, 2015.
ISSN:XPaís de publica??o:England
Idioma:engResumo:BACKGROUND: The 39 mammalian Hox genes show problematic patterns of functional overlap. In order to more fully define the developmental roles of Hox genes it is necessary to remove multiple combinations of paralogous and flanking genes. In addition, the downstream molecular pathways regulated by Hox genes during limb development remain incompletely delineated. RESULTS: In this report we examine limb development in mice with frameshift mutations in six Hox genes, Hoxa9,10,11 and Hoxd9,10,11. The mice were made with a novel recombineering method that allows the simultaneous targeting of frameshift mutations into multiple flanking genes. The Hoxa9,10,11 (-/-) /Hoxd9,10,11 (-/-) mutant mice show a reduced ulna and radius that is more severe than seen in Hoxa11 (-/-)/Hoxd11 (-/-) mice, indicating a minor role for the flanking Hox9,10 genes in zeugopod development, as well as their primary function in stylopod development. The mutant mice also show severe reduction of Shh expression in the zone of polarizing activity, and decreased Fgf8 expression in the apical ectodermal ridge, thereby better defining the roles of these specific Hox genes in the regulation of critical signaling centers during limb development. Importantly, we also used laser capture microdissection coupled with RNA-Seq to characterize the gene expression programs in wild type and mutant limbs. Resting, proliferative and hypertrophic compartments of E15.5 forelimb zeugopods were examined. The results provide an RNA-Seq characterization of the progression of gene expression patterns during normal endochondral bone formation. In addition of the Hox mutants showed strongly altered expression of Pknox2, Zfp467, Gdf5, Bmpr1b, Dkk3, Igf1, Hand2, Shox2, Runx3, Bmp7 and Lef1, all of which have been previously shown to play important roles in bone formation. CONCLUSIONS: The recombineering based frameshift mutation of the six flanking and paralogous Hoxa9,10,11 and Hoxd9,10,11 genes provides a resource for the analysis of their overlapping functions. Analysis of the Hoxa9,10,11 (-/-) /Hoxd9,10,11 (-/-) mutant limbs confirms and extends the results of previous studies using mice with Hox mutations in single paralogous groups or with entire Hox cluster deletions. The RNA-Seq analysis of specific compartments of the normal and mutant limbs defines the multiple key perturbed pathways downstream of these Hox genes.
Tipo de publica??o: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
Nome de subst?ncia:0 (Homeodomain Proteins)
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Autor:Wu R; Liu Q; Meng S; Zhang P; Liang DEndere?o:State Key Laboratory of Biocontrol, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, People's Republic of China. urgaa.....
Título:Hox cluster characterization of Banna caecilian (Ichthyophis bannanicus) provides hints for slow evolution of its genome.
Fonte:BMC G 16:468, 2015.
ISSN:País de publica??o:England
Idioma:engResumo:BACKGROUND: Caecilians, with a discrete lifestyle, are the least explored group of amphibians. Though with distinct traits, many aspects of their biology are poorly investigated. Obtaining the caecilian genomic sequences will offer new perspectives and aid the fundamental studies in caecilian biology. The caecilian genomic sequences are also important and practical in the comparative genomics of amphibians. Currently, however, only sparse genomic sequences of caecilians are available. Hox genes, an old family of transcription factors playing central roles in the establishment of metazoan body plan. Understanding their structure and genomic organization may provide insights into the animal's genome, which is valuable for animals without a sequenced genome. RESULTS: We sequenced and characterized the Hox clusters of Banna caecilian (Ichthyophis bannanicus) with a strategy combining long range PCR and genome walking. We obtained the majority of the four caecilian Hox clusters and identified 39 Hox genes, 5 microRNA genes and 1 pseudogene (ψHoxD12). There remained seven intergenic gaps we were unable to fill. From the obtained sequences, the caecilian Hox clusters contained less repetitive sequences and more conserved noncoding elements (CNEs) than the frog counterparts. We found that caecilian and coelacanth shared many more CNEs than frog and coelacanth did. Relative rate of sequence evolution showed that caecilian Hox genes evolved significantly more slowly than the other tetrapod species used in this study and were comparable to the slowly evolving coelacanth Hox genes. Phylogenetic tree of the four Hox clusters also revealed shorter branch length especially for the caecilian HoxA, HoxB and HoxD clusters. These features of the caecilian Hox clusters suggested a slowly evolving genome, which was supported by further analysis of a large orthologous protein dataset. CONCLUSIONS: Our analyses greatly extended the knowledge about the caecilian Hox clusters from previous PCR surveys. From the obtained Hox sequences and the orthologous protein dataset, the caecilian Hox loci and its genome appear evolving comparatively slowly. As the basal lineage of amphibians and land vertebrate, this characteristic of the caecilian genome is valuable in the study concerning the genome biology and evolution of amphibians and early tetrapods.
Tipo de publica??o: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
Nome de subst?ncia:0 (MicroRNAs)
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Autor:Zuniga AEndere?o:Developmental Genetics, Department of Biomedicine, University of Basel, Mattenstrasse 28, Basel CH-4058, Switzerland Aimee.Zuniga@unibas.ch.
Título:Next generation limb development and evolution: old questions, new perspectives.
Fonte:D 142(22):15 Nov 15.
ISSN:País de publica??o:England
Idioma:engResumo:The molecular analysis of limb bud development in vertebrates continues to fuel our understanding of the gene regulatory networks that orchestrate the patterning, proliferation and differentiation of embryonic progenitor cells. In recent years, systems biology approaches have moved our understanding of the molecular control of limb organogenesis to the next level by incorporating next generation 'omics' approaches, analyses of chromatin architecture, enhancer-promoter interactions and gene network simulations based on quantitative datasets into experimental analyses. This Review focuses on the insights these studies have given into the gene regulatory networks that govern limb development and into the fin-to-limb transition and digit reductions that occurred during the evolutionary diversification of tetrapod limbs.
Tipo de publica??o: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
Nome de subst?ncia:0 (Hedgehog Proteins)
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Autor:Waardenberg AJ; Basset SD; Bouveret R; Harvey RPEndere?o:Victor Chang Cardiac Research Institute, Darlinghurst, NSW, 2010, Australia. awaardenberg@cmri.org.au....
Título:CompGO: an R package for comparing and visualizing Gene Ontology enrichment differences between DNA binding experiments.
Fonte:BMC B 16:275, 2015.
ISSN:País de publica??o:England
Idioma:engResumo:BACKGROUND: Gene ontology (GO) enrichment is commonly used for inferring biological meaning from systems biology experiments. However, determining differential GO and pathway enrichment between DNA-binding experiments or using the GO structure to classify experiments has received little attention. RESULTS: Herein, we present a bioinformatics tool, CompGO, for identifying Differentially Enriched Gene Ontologies, called DiEGOs, and pathways, through the use of a z-score derivation of log odds ratios, and visualizing these differences at GO and pathway level. Through public experimental data focused on the cardiac transcription factor NKX2-5, we illustrate the problems associated with comparing GO enrichments between experiments using a simple overlap approach. CONCLUSIONS: We have developed an R/Bioconductor package, CompGO, which implements a new statistic normally used in epidemiological studies for performing comparative GO analyses and visualizing comparisons from . BED data containing genomic coordinates as well as gene lists as inputs. We justify the statistic through inclusion of experimental data and compare to the commonly used overlap method. CompGO is freely available as a R/Bioconductor package enabling easy integration into existing pipelines and is available at: http://www.bioconductor.org/packages/release/bioc/html/CompGO.html packages/release/bioc/html/CompGO.html.
Tipo de publica??o: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
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Autor:Liu Y; Ma D; Ji CEndere?o:Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
Título:Zinc fingers and homeoboxes family in human diseases.
Fonte:Cancer Gene T 22(5):223-6, 2015 May.
ISSN:País de publica??o:England
Idioma:engResumo:The zinc-fingers and homeoboxes (ZHX) family is a group of nuclear homodimeric transcriptional repressors that interact with a subunit of nuclear factor-Y (NF-YA) and contain two C2H2-type zinc fingers and five homeobox DNA-binding domains. The members of ZHX family form homodimers or heterodimers with other members or a subunit of NF-YA to repress transcription. ZHX family members function in hematopoietic cell development and differentiation, and neural progenitor maintenance. Dysfunction of ZHX family members correlates with the development and progression of various diseases, including hepatocellular carcinoma (HCC), hematological diseases, neurological diseases and glomerular diseases. Furthermore, low expression of ZHX is associated with poor prognosis in malignancies. This review provides an update on the role of ZHX family in development and its function in cancer, with special emphasis on HCC and hematological malignant diseases.
Tipo de publica??o: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
Nome de subst?ncia:0 (Homeodomain Proteins)
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Autor:Huang J; Zhang H; Wang X; Dobbs KB; Yao J; Qin G; Whitworth K; Walters EM; Prather RS; Zhao JEndere?o:State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China University of Chinese Academy of Sciences, Beijing, China....
Título:Impairment of preimplantation porcine embryo development by histone demethylase KDM5B knockdown through disturbance of bivalent H3K4me3-H3K27me3 modifications.
Fonte:Biol R 92(3):72, 2015 Mar.
ISSN:País de publica??o:United States
Idioma:engResumo:KDM5B (JARID1B/PLU1) is a H3K4me2/3 histone demethylase that is implicated in cancer development and proliferation and is also indispensable for embryonic stem cell self-renewal, cell fate, and murine embryonic development. However, little is known about the role of KDM5B during preimplantation embryo development. Here we show that KDM5B is critical to porcine preimplantation development. KDM5B was found to be expressed in a stage-specific manner, consistent with demethylation of H3K4me3, with the highest expression being observed from the 4-cell to the blastocyst stages. Knockdown of KDM5B by morpholino antisense oligonucleotides injection impaired porcine embryo development to the blastocyst stage. The impairment of embryo development might be caused by increased expression of H3K4me3 at the 4-cell and blastocyst stages, which disturbs the balance of bivalent H3K4me3-H3K27me3 modifications at the blastocyst stage. Decreased abundance of H3K27me3 at blastocyst stage activates multiple members of homeobox genes (HOX), which need to be silenced for faithful embryo development. Additionally, the histone demethylase KDM6A was found to be upregulated by knockdown of KDM5B, which indicated it was responsible for the decreased abundance of H3K27me3 at the blastocyst stage. The transcriptional levels of Ten-Eleven Translocation gene family members (TET1, TET2, and TET3) are found to be increased by knockdown of KDM5B, which indicates cross talk between histone modifications and DNA methylation. The studies above indicate that KDM5B is required for porcine embryo development through regulating the balance of bivalent H3K4me3-H3K27me3 modifications.
Tipo de publica??o: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
Nome de subst?ncia:0 (DNA-Binding Proteins); EC 1.14.11.- (Histone Demethylases); EC 1.14.11.- (Jumonji Domain-Containing Histone Demethylases)
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Autor:Fabre PJ; Benke A; Joye E; Nguyen Huynh TH; Manley S; Duboule DEndere?o:School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, S...
Título:Nanoscale spatial organization of the HoxD gene cluster in distinct transcriptional states.
Fonte:Proc Natl Acad Sci U S A; 112(45):15 Nov 10.
ISSN:País de publica??o:United States
Idioma:engResumo:Chromatin condensation plays an important role in the regulation of gene expression. Recently, it was shown that the transcriptional activation of Hoxd genes during vertebrate digit development involves modifications in 3D interactions within and around the HoxD gene cluster. This reorganization follows a global transition from one set of regulatory contacts to another, between two topologically associating domains (TADs) located on either side of the HoxD locus. Here, we use 3D DNA FISH to assess the spatial organization of chromatin at and around the HoxD gene cluster and report that although the two TADs are tightly associated, they appear as spatially distinct units. We measured the relative position of genes within the cluster and found that they segregate over long distances, suggesting that a physical elongation of the HoxD cluster can occur. We analyzed this possibility by super-resolution imaging (STORM) and found that tissues with distinct transcriptional activity exhibit differing degrees of elongation. We also observed that the morphological change of the HoxD cluster in developing digits is associated with its position at the boundary between the two TADs. Such variations in the fine-scale architecture of the gene cluster suggest causal links among its spatial configuration, transcriptional activation, and the flanking chromatin context.
Tipo de publica??o: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
Nome de subst?ncia:0 (Chromatin)
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Autor:Levine M; Vicente CTítulo:An interview with Mike Levine.
Fonte:D 142(20):15 Oct 15.
ISSN:País de publica??o:England
Idioma:engResumo:Mike Levine, director of the Lewis-Sigler Institute for Integrative Genomics at Princeton University, is a developmental biologist who has dedicated his career to understanding how gene expression is regulated during development. Some of his most significant research, such as the co-discovery of the homeobox genes and his work on even skipped stripe 2, was performed in Drosophila, but he has since branched out to Ciona intestinalis, which he is using as a model to understand how vertebrate features have evolved. We had a lively chat with Mike at this year's Society for Developmental Biology (SDB) meeting, where he was awarded the Edwin Grant Conklin Medal.
Tipo de publica??o: HISTORICAL ARTICLE; INTERVIEW; PORTRAITS
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Autor:Javeed N; Tardi NJ; Maher M; Singari S; Edwards KAEndere?o:School of Biological Sciences, Illinois State University, Normal, Illinois....
Título:Controlled expression of Drosophila homeobox loci using the Hostile takeover system.
Fonte:Dev D 244(6):808-25, 2015 Jun.
ISSN:País de publica??o:United States
Idioma:engResumo:BACKGROUND: Hostile takeover (Hto) is a Drosophila protein trapping system that allows the investigator to both induce a gene and tag its product. The Hto transposon carries a GAL4-regulated promoter expressing an exon encoding a FLAG-mCherry tag. Upon expression, the Hto exon can splice to a downstream genomic exon, generating a fusion transcript and tagged protein. RESULTS: Using rough-eye phenotypic screens, Hto inserts were recovered at eight homeobox or Pax loci: cut, Drgx/CG34340, Pox neuro, araucan, shaven/D-Pax2, Zn finger homeodomain 2, Sex combs reduced (Scr), and the abdominal-A region. The collection yields diverse misexpression phenotypes. Ectopic Drgx was found to alter the cytoskeleton and cell adhesion in ovary follicle cells. Hto expression of cut, araucan, or shaven gives phenotypes similar to those of the corresponding UAS-cDNA constructs. The cut and Pox neuro phenotypes are suppressed by the corresponding RNAi constructs. The Scr and abdominal-A inserts do not make fusion proteins, but may act by chromatin- or RNA-based mechanisms. CONCLUSIONS: Hto can effectively express tagged homeodomain proteins from t the Minos vector allows inserts to be obtained even in transposon cold-spots. Hto screens may recover homeobox genes at high rates because they are particularly sensitive to misexpression.
Tipo de publica??o: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
Nome de subst?ncia:0 (DNA Transposable Elements); 0 (DNA, Complementary); 0 (DNA-Binding Proteins); 0 (Drosophila Proteins); 0 (Eye Proteins); 0 (GAL4 protein, S cerevisiae); 0 (Homeodomain Proteins); 0 (Luminescent Proteins); 0 (Recombinant Fusion Proteins); 0 (Saccharomyces cerevisiae Proteins); 0 (Transcription Factors); 0 (red fluorescent protein)
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Autor:Chan C; Jayasekera S; Kao B; Páramo M; von Grotthuss M; Ranz JMEndere?o:Department of Ecology and Evolutionary Biology, University of California Irvine, Irvine, California 92697, USA....
Título:Remodelling of a homeobox gene cluster by multiple independent gene reunions in Drosophila.
Fonte:Nat C 6:.
ISSN:País de publica??o:England
Idioma:engResumo:Genome clustering of homeobox genes is often thought to reflect arrangements of tandem gene duplicates maintained by advantageous coordinated gene regulation. Here we analyse the chromosomal organization of the NK homeobox genes, presumed to be part of a single cluster in the Bilaterian ancestor, across 20 arthropods. We find that the ProtoNK cluster was extensively fragmented in some lineages, showing that NK clustering in Drosophila species does not reflect selectively maintained gene arrangements. More importantly, the arrangement of NK and neighbouring genes across the phylogeny supports that, in two instances within the Drosophila genus, some cluster remnants became reunited via large-scale chromosomal rearrangements. Simulated scenarios of chromosome evolution indicate that these reunion events are unlikely unless the genome neighbourhoods harbouring the participating genes tend to colocalize in the nucleus. Our results underscore how mechanisms other than tandem gene duplication can result in paralogous gene clustering during genome evolution.
Tipo de publica??o: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
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