Genomic occupancy of Runx2 with global expression profiling identifies a novel dimension to control of osteoblastogenesis.

Abstract:

BACKGROUND:Osteogenesis is a highly regulated developmental process and continues during the turnover and repair of mature bone. Runx2, the master regulator of osteoblastogenesis, directs a transcriptional program essential for bone formation through genetic and epigenetic mechanisms. While individual Runx2 gene targets have been identified, further insights into the broad spectrum of Runx2 functions required for osteogenesis are needed. RESULTS:By performing genome-wide characterization of Runx2 binding at the three major stages of osteoblast differentiation--proliferation, matrix deposition and mineralization--we identify Runx2-dependent regulatory networks driving bone formation. Using chromatin immunoprecipitation followed by high-throughput sequencing over the course of these stages, we identify approximately 80,000 significantly enriched regions of Runx2 binding throughout the mouse genome. These binding events exhibit distinct patterns during osteogenesis, and are associated with proximal promoters and also non-promoter regions: upstream, introns, exons, transcription termination site regions, and intergenic regions. These peaks were partitioned into clusters that are associated with genes in complex biological processes that support bone formation. Using Affymetrix expression profiling of differentiating osteoblasts depleted of Runx2, we identify novel Runx2 targets including Ezh2, a critical epigenetic regulator; Crabp2, a retinoic acid signaling component; Adamts4 and Tnfrsf19, two remodelers of the extracellular matrix. We demonstrate by luciferase assays that these novel biological targets are regulated by Runx2 occupancy at non-promoter regions. CONCLUSIONS:Our data establish that Runx2 interactions with chromatin across the genome reveal novel genes, pathways and transcriptional mechanisms that contribute to the regulation of osteoblastogenesis.

journal_name

Genome Biol

journal_title

Genome biology

authors

Wu H,Whitfield TW,Gordon JA,Dobson JR,Tai PW,van Wijnen AJ,Stein JL,Stein GS,Lian JB

doi

10.1186/gb-2014-15-3-r52

subject

Has Abstract

pub_date

2014-03-21 00:00:00

pages

R52

issue

3

eissn

1474-7596

issn

1474-760X

pii

gb-2014-15-3-r52

journal_volume

15

pub_type

杂志文章
  • A prediction-based resampling method for estimating the number of clusters in a dataset.

    abstract:BACKGROUND:Microarray technology is increasingly being applied in biological and medical research to address a wide range of problems, such as the classification of tumors. An important statistical problem associated with tumor classification is the identification of new tumor classes using gene-expression profiles. Tw...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2002-3-7-research0036

    authors: Dudoit S,Fridlyand J

    更新日期:2002-06-25 00:00:00

  • The first whole genome and transcriptome of the cinereous vulture reveals adaptation in the gastric and immune defense systems and possible convergent evolution between the Old and New World vultures.

    abstract:BACKGROUND:The cinereous vulture, Aegypius monachus, is the largest bird of prey and plays a key role in the ecosystem by removing carcasses, thus preventing the spread of diseases. Its feeding habits force it to cope with constant exposure to pathogens, making this species an interesting target for discovering functio...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/s13059-015-0780-4

    authors: Chung O,Jin S,Cho YS,Lim J,Kim H,Jho S,Kim HM,Jun J,Lee H,Chon A,Ko J,Edwards J,Weber JA,Han K,O'Brien SJ,Manica A,Bhak J,Paek WK

    更新日期:2015-10-21 00:00:00

  • Characterization of the expression ratio noise structure in high-density oligonucleotide arrays.

    abstract:BACKGROUND:High-density oligonucleotide microarrays provide a powerful tool for assessing differential mRNA expression levels. Characterizing the noise resulting from the enzymatic and hybridization steps, called type I noise, is essential for attributing significance measures to the differential expression scores. We ...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:

    authors: Naef F,Hacker CR,Patil N,Magnasco M

    更新日期:2002-01-01 00:00:00

  • Mechanisms of aging in senescence-accelerated mice.

    abstract:BACKGROUND:Progressive neurological dysfunction is a key aspect of human aging. Because of underlying differences in the aging of mice and humans, useful mouse models have been difficult to obtain and study. We have used gene-expression analysis and polymorphism screening to study molecular senescence of the retina and...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2005-6-6-r48

    authors: Carter TA,Greenhall JA,Yoshida S,Fuchs S,Helton R,Swaroop A,Lockhart DJ,Barlow C

    更新日期:2005-01-01 00:00:00

  • Immunostaining of modified histones defines high-level features of the human metaphase epigenome.

    abstract:BACKGROUND:Immunolabeling of metaphase chromosome spreads can map components of the human epigenome at the single cell level. Previously, there has been no systematic attempt to explore the potential of this approach for epigenomic mapping and thereby to complement approaches based on chromatin immunoprecipitation (ChI...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2010-11-11-r110

    authors: Terrenoire E,McRonald F,Halsall JA,Page P,Illingworth RS,Taylor AM,Davison V,O'Neill LP,Turner BM

    更新日期:2010-01-01 00:00:00

  • Accurate and equitable medical genomic analysis requires an understanding of demography and its influence on sample size and ratio.

    abstract::In a recent study, Petrovski and Goldstein reported that (non-Finnish) Europeans have significantly fewer nonsynonymous singletons in Online Mendelian Inheritance in Man (OMIM) disease genes compared with Africans, Latinos, South Asians, East Asians, and other unassigned non-Europeans. We use simulations of Exome Aggr...

    journal_title:Genome biology

    pub_type: 评论,信件

    doi:10.1186/s13059-017-1172-8

    authors: Kessler MD,O'Connor TD

    更新日期:2017-02-27 00:00:00

  • Growth-rate regulated genes have profound impact on interpretation of transcriptome profiling in Saccharomyces cerevisiae.

    abstract:BACKGROUND:Growth rate is central to the development of cells in all organisms. However, little is known about the impact of changing growth rates. We used continuous cultures to control growth rate and studied the transcriptional program of the model eukaryote Saccharomyces cerevisiae, with generation times varying be...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2006-7-11-r107

    authors: Regenberg B,Grotkjaer T,Winther O,Fausbøll A,Akesson M,Bro C,Hansen LK,Brunak S,Nielsen J

    更新日期:2006-01-01 00:00:00

  • Chromatin accessibility reveals insights into androgen receptor activation and transcriptional specificity.

    abstract:BACKGROUND:Epigenetic mechanisms such as chromatin accessibility impact transcription factor binding to DNA and transcriptional specificity. The androgen receptor (AR), a master regulator of the male phenotype and prostate cancer pathogenesis, acts primarily through ligand-activated transcription of target genes. Altho...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2012-13-10-r88

    authors: Tewari AK,Yardimci GG,Shibata Y,Sheffield NC,Song L,Taylor BS,Georgiev SG,Coetzee GA,Ohler U,Furey TS,Crawford GE,Febbo PG

    更新日期:2012-10-03 00:00:00

  • Long mRNAs coding for yeast mitochondrial proteins of prokaryotic origin preferentially localize to the vicinity of mitochondria.

    abstract:BACKGROUND:Subcellular messenger RNA localization is important in most eukaryotic cells, even in unicellular organisms like yeast for which this process has been underestimated. Microarrays are rarely used to study subcellular mRNA localization at whole-genome level, but can be adapted to that purpose. This work focuse...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2003-4-7-r44

    authors: Sylvestre J,Vialette S,Corral Debrinski M,Jacq C

    更新日期:2003-01-01 00:00:00

  • Species-wide distribution of highly polymorphic minisatellite markers suggests past and present genetic exchanges among house mouse subspecies.

    abstract:BACKGROUND:Four hypervariable minisatellite loci were scored on a panel of 116 individuals of various geographical origins representing a large part of the diversity present in house mouse subspecies. Internal structures of alleles were determined by minisatellite variant repeat mapping PCR to produce maps of interming...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2007-8-5-r80

    authors: Bonhomme F,Rivals E,Orth A,Grant GR,Jeffreys AJ,Bois PR

    更新日期:2007-01-01 00:00:00

  • An improved method for detecting and delineating genomic regions with altered gene expression in cancer.

    abstract::Genomic regions with altered gene expression are a characteristic feature of cancer cells. We present a novel method for identifying such regions in gene expression maps. This method is based on total variation minimization, a classical signal restoration technique. In systematic evaluations, we show that our method c...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2008-9-1-r13

    authors: Nilsson B,Johansson M,Heyden A,Nelander S,Fioretos T

    更新日期:2008-01-21 00:00:00

  • Chemical genomics in yeast.

    abstract::Many drugs have unknown, controversial or multiple mechanisms of action. Four recent 'chemical genomic' studies, using genome-scale collections of yeast gene deletions that were either arrayed or barcoded, have presented complementary approaches to identifying gene-drug and pathway-drug interactions. ...

    journal_title:Genome biology

    pub_type: 杂志文章,评审

    doi:10.1186/gb-2004-5-9-240

    authors: Brenner C

    更新日期:2004-01-01 00:00:00

  • quantro: a data-driven approach to guide the choice of an appropriate normalization method.

    abstract::Normalization is an essential step in the analysis of high-throughput data. Multi-sample global normalization methods, such as quantile normalization, have been successfully used to remove technical variation. However, these methods rely on the assumption that observed global changes across samples are due to unwanted...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/s13059-015-0679-0

    authors: Hicks SC,Irizarry RA

    更新日期:2015-06-04 00:00:00

  • Comprehensive assessment of computational algorithms in predicting cancer driver mutations.

    abstract:BACKGROUND:The initiation and subsequent evolution of cancer are largely driven by a relatively small number of somatic mutations with critical functional impacts, so-called driver mutations. Identifying driver mutations in a patient's tumor cells is a central task in the era of precision cancer medicine. Over the deca...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/s13059-020-01954-z

    authors: Chen H,Li J,Wang Y,Ng PK,Tsang YH,Shaw KR,Mills GB,Liang H

    更新日期:2020-02-20 00:00:00

  • Selection in the evolution of gene duplications.

    abstract:BACKGROUND:Gene duplications have a major role in the evolution of new biological functions. Theoretical studies often assume that a duplication per se is selectively neutral and that, following a duplication, one of the gene copies is freed from purifying (stabilizing) selection, which creates the potential for evolut...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2002-3-2-research0008

    authors: Kondrashov FA,Rogozin IB,Wolf YI,Koonin EV

    更新日期:2002-01-01 00:00:00

  • Whole genome DNA sequencing provides an atlas of somatic mutagenesis in healthy human cells and identifies a tumor-prone cell type.

    abstract:BACKGROUND:The lifelong accumulation of somatic mutations underlies age-related phenotypes and cancer. Mutagenic forces are thought to shape the genome of aging cells in a tissue-specific way. Whole genome analyses of somatic mutation patterns, based on both types and genomic distribution of variants, can shed light on...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/s13059-019-1892-z

    authors: Franco I,Helgadottir HT,Moggio A,Larsson M,Vrtačnik P,Johansson A,Norgren N,Lundin P,Mas-Ponte D,Nordström J,Lundgren T,Stenvinkel P,Wennberg L,Supek F,Eriksson M

    更新日期:2019-12-18 00:00:00

  • iRegNet3D: three-dimensional integrated regulatory network for the genomic analysis of coding and non-coding disease mutations.

    abstract::The mechanistic details of most disease-causing mutations remain poorly explored within the context of regulatory networks. We present a high-resolution three-dimensional integrated regulatory network (iRegNet3D) in the form of a web tool, where we resolve the interfaces of all known transcription factor (TF)-TF, TF-D...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/s13059-016-1138-2

    authors: Liang S,Tippens ND,Zhou Y,Mort M,Stenson PD,Cooper DN,Yu H

    更新日期:2017-01-18 00:00:00

  • A basis for a visual language for describing, archiving and analyzing functional models of complex biological systems.

    abstract:BACKGROUND:We propose that a computerized, internet-based graphical description language for systems biology will be essential for describing, archiving and analyzing complex problems of biological function in health and disease. RESULTS:We outline here a conceptual basis for designing such a language and describe Bio...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2001-2-4-research0012

    authors: Cook DL,Farley JF,Tapscott SJ

    更新日期:2001-01-01 00:00:00

  • Integrating systems biology data to yield functional genomics insights.

    abstract::A report of the recent EMBO Conference 'From Functional Genomics to Systems Biology' held at the EMBL Advanced Training Centre, Heidelberg, Germany, 13-16 November 2010. ...

    journal_title:Genome biology

    pub_type:

    doi:10.1186/gb-2011-12-1-302

    authors: Fordyce P,Ingolia N

    更新日期:2011-01-01 00:00:00

  • NicE-seq: high resolution open chromatin profiling.

    abstract::Open chromatin profiling integrates information across diverse regulatory elements to reveal the transcriptionally active genome. Tn5 transposase and DNase I sequencing-based methods prefer native or high cell numbers. Here, we describe NicE-seq (nicking enzyme assisted sequencing) for high-resolution open chromatin p...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/s13059-017-1247-6

    authors: Ponnaluri VKC,Zhang G,Estève PO,Spracklin G,Sian S,Xu SY,Benoukraf T,Pradhan S

    更新日期:2017-06-28 00:00:00

  • Surveying genome replication.

    abstract::Two recent studies have added microarrays to the toolkit used to analyze the origins of replication in yeast chromosomes, providing a fuller picture of how genomic DNA replication is organized. ...

    journal_title:Genome biology

    pub_type: 杂志文章,评审

    doi:10.1186/gb-2002-3-6-reviews1016

    authors: Kearsey S

    更新日期:2002-01-01 00:00:00

  • Comparative genomics of the pathogenic ciliate Ichthyophthirius multifiliis, its free-living relatives and a host species provide insights into adoption of a parasitic lifestyle and prospects for disease control.

    abstract:BACKGROUND:Ichthyophthirius multifiliis, commonly known as Ich, is a highly pathogenic ciliate responsible for 'white spot', a disease causing significant economic losses to the global aquaculture industry. Options for disease control are extremely limited, and Ich's obligate parasitic lifestyle makes experimental stud...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2011-12-10-r100

    authors: Coyne RS,Hannick L,Shanmugam D,Hostetler JB,Brami D,Joardar VS,Johnson J,Radune D,Singh I,Badger JH,Kumar U,Saier M,Wang Y,Cai H,Gu J,Mather MW,Vaidya AB,Wilkes DE,Rajagopalan V,Asai DJ,Pearson CG,Findly RC,Di

    更新日期:2011-10-17 00:00:00

  • A comparison of programmed cell death between species.

    abstract::Key components of the programmed cell death pathway are conserved between Caenorhabditis elegans, Drosophila melanogaster and humans. The search for additional homologs has been facilitated by the availability of the entire genomic sequence for each of these organisms. ...

    journal_title:Genome biology

    pub_type: 杂志文章,评审

    doi:10.1186/gb-2000-1-3-reviews0003

    authors: Tittel JN,Steller H

    更新日期:2000-01-01 00:00:00

  • Evidence from comparative genomics for a complete sexual cycle in the 'asexual' pathogenic yeast Candida glabrata.

    abstract:BACKGROUND:Candida glabrata is a pathogenic yeast of increasing medical concern. It has been regarded as asexual since it was first described in 1917, yet phylogenetic analyses have revealed that it is more closely related to sexual yeasts than other Candida species. We show here that the C. glabrata genome contains ma...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2003-4-2-r10

    authors: Wong S,Fares MA,Zimmermann W,Butler G,Wolfe KH

    更新日期:2003-01-01 00:00:00

  • ReMixT: clone-specific genomic structure estimation in cancer.

    abstract::Somatic evolution of malignant cells produces tumors composed of multiple clonal populations, distinguished in part by rearrangements and copy number changes affecting chromosomal segments. Whole genome sequencing mixes the signals of sampled populations, diluting the signals of clone-specific aberrations, and complic...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/s13059-017-1267-2

    authors: McPherson AW,Roth A,Ha G,Chauve C,Steif A,de Souza CPE,Eirew P,Bouchard-Côté A,Aparicio S,Sahinalp SC,Shah SP

    更新日期:2017-07-27 00:00:00

  • A simple genetic basis of adaptation to a novel thermal environment results in complex metabolic rewiring in Drosophila.

    abstract:BACKGROUND:Population genetic theory predicts that rapid adaptation is largely driven by complex traits encoded by many loci of small effect. Because large-effect loci are quickly fixed in natural populations, they should not contribute much to rapid adaptation. RESULTS:To investigate the genetic architecture of therm...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/s13059-018-1503-4

    authors: Mallard F,Nolte V,Tobler R,Kapun M,Schlötterer C

    更新日期:2018-08-20 00:00:00

  • Modeling double strand break susceptibility to interrogate structural variation in cancer.

    abstract:BACKGROUND:Structural variants (SVs) are known to play important roles in a variety of cancers, but their origins and functional consequences are still poorly understood. Many SVs are thought to emerge from errors in the repair processes following DNA double strand breaks (DSBs). RESULTS:We used experimentally quantif...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/s13059-019-1635-1

    authors: Ballinger TJ,Bouwman BAM,Mirzazadeh R,Garnerone S,Crosetto N,Semple CA

    更新日期:2019-02-08 00:00:00

  • Demystifying "drop-outs" in single-cell UMI data.

    abstract::Many existing pipelines for scRNA-seq data apply pre-processing steps such as normalization or imputation to account for excessive zeros or "drop-outs." Here, we extensively analyze diverse UMI data sets to show that clustering should be the foremost step of the workflow. We observe that most drop-outs disappear once ...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/s13059-020-02096-y

    authors: Kim TH,Zhou X,Chen M

    更新日期:2020-08-06 00:00:00

  • EpiGRAPH: user-friendly software for statistical analysis and prediction of (epi)genomic data.

    abstract::The EpiGRAPH web service http://epigraph.mpi-inf.mpg.de/ enables biologists to uncover hidden associations in vertebrate genome and epigenome datasets. Users can upload sets of genomic regions and EpiGRAPH will test multiple attributes (including DNA sequence, chromatin structure, epigenetic modifications and evolutio...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2009-10-2-r14

    authors: Bock C,Halachev K,Büch J,Lengauer T

    更新日期:2009-02-10 00:00:00

  • Zinc finger nuclease-based double-strand breaks attenuate malaria parasites and reveal rare microhomology-mediated end joining.

    abstract:BACKGROUND:Genome editing of malaria parasites is key to the generation of live attenuated parasites used in experimental vaccination approaches. DNA repair in Plasmodium generally occurs only through homologous recombination. This has been used to generate transgenic parasites that lack one to three genes, leading to ...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/s13059-015-0811-1

    authors: Singer M,Marshall J,Heiss K,Mair GR,Grimm D,Mueller AK,Frischknecht F

    更新日期:2015-11-17 00:00:00