Abstract:
:Spatially distinct gene expression profiles in neural stem cells (NSCs) are a prerequisite to the formation of neuronal diversity, but how these arise from the regulatory interactions between chromatin accessibility and transcription factor activity has remained unclear. Here, we demonstrate that, despite their distinct gene expression profiles, NSCs of the mouse cortex and spinal cord share the majority of their DNase I hypersensitive sites (DHSs). Regardless of this similarity, domain-specific gene expression is highly correlated with the relative accessibility of associated DHSs, as determined by sequence read density. Notably, the binding pattern of the general NSC transcription factor SOX2 is also largely cell type specific and coincides with an enrichment of LHX2 motifs in the cortex and HOXA9 motifs in the spinal cord. Interestingly, in a zebrafish reporter gene system, these motifs were critical determinants of patterned gene expression along the rostral-caudal axis. Our findings establish a predictive model for patterned NSC gene expression, whereby domain-specific expression of LHX2 and HOX proteins act on their target motifs within commonly accessible cis-regulatory regions to specify SOX2 binding. In turn, this binding correlates strongly with these DHSs relative accessibility-a robust predictor of neighboring gene expression.
journal_name
Genome Resjournal_title
Genome researchauthors
Hagey DW,Zaouter C,Combeau G,Lendahl MA,Andersson O,Huss M,Muhr Jdoi
10.1101/gr.203513.115subject
Has Abstractpub_date
2016-07-01 00:00:00pages
908-17issue
7eissn
1088-9051issn
1549-5469pii
gr.203513.115journal_volume
26pub_type
杂志文章相关文献
GENOME RESEARCH文献大全abstract::Mycoplasma mycoides subsp. mycoidesSC (MmymySC)is the etiological agent of contagious bovine pleuropneumonia (CBPP), a highly contagious respiratory disease in cattle. The genome of Mmymy SC type strain PG1(T) has been sequenced to map all the genes and to facilitate further studies regarding the cell function of the ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.1673304
更新日期:2004-02-01 00:00:00
abstract::We find that the degree of impairment of protein function by missense variants is predictable by comparative sequence analysis alone. The applicable range of impairment is not confined to binary predictions that distinguish normal from deleterious variants, but extends continuously from mild to severe effects. The acc...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.3804205
更新日期:2005-07-01 00:00:00
abstract::Lemurs and the other strepsirrhine primates are of great interest to the primate genomics community due to their phylogenetic placement as the sister lineage to all other primates. Previous attempts to resolve the phylogeny of lemurs employed limited mitochondrial or small nuclear data sets, with many relationships po...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.7265208
更新日期:2008-03-01 00:00:00
abstract::Current methods struggle to reconstruct and visualize the genomic relationships of large numbers of bacterial genomes. GrapeTree facilitates the analyses of large numbers of allelic profiles by a static "GrapeTree Layout" algorithm that supports interactive visualizations of large trees within a web browser window. Gr...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.232397.117
更新日期:2018-09-01 00:00:00
abstract::Recent advances in genome research have accelerated the process of locating candidate genes and the variable sites within them and have simplified the task of genotype measurement. The development of statistical and computational strategies to utilize information on hundreds -- soon thousands -- of variable loci to in...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.172901
更新日期:2001-03-01 00:00:00
abstract::Pollen, the male gametophyte of flowering plants, represents an ideal biological system to study developmental processes, such as cell polarity, tip growth, and morphogenesis. Upon hydration, the metabolically quiescent pollen rapidly switches to an active state, exhibiting extremely fast growth. This rapid switch req...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.089060.108
更新日期:2009-10-01 00:00:00
abstract::Long noncoding RNAs (lncRNAs) play a conserved role in regulating gene expression, chromatin dynamics, and cell differentiation. They serve as a platform for RNA interference (RNAi)-mediated heterochromatin formation or DNA methylation in many eukaryotic organisms. We found in Schizosaccharomyces pombe that heterochro...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.216986.116
更新日期:2017-07-01 00:00:00
abstract::Genome-wide association studies (GWAS) have consistently implicated noncoding variation within the TCF7L2 locus with type 2 diabetes (T2D) risk. While this locus represents the strongest genetic determinant for T2D risk in humans, it remains unclear how these noncoding variants affect disease etiology. To test the hyp...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.123745.111
更新日期:2011-09-01 00:00:00
abstract::Mutation rates of microsatellites vary greatly among loci. The causes of this heterogeneity remain largely enigmatic yet are crucial for understanding numerous human neurological diseases and genetic instability in cancer. In this first genome-wide study, the relative contributions of intrinsic features and regional g...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.7113408
更新日期:2008-01-01 00:00:00
abstract::The identification and interpretation of the regulatory signals within the human genome remain among the greatest goals and most difficult challenges in genome analysis. The ability to predict the temporal and spatial control of transcription is likely to require a combination of methods to address the contribution of...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.180601
更新日期:2001-09-01 00:00:00
abstract::LSH, a member of the SNF2 family of chromatin remodeling ATPases encoded by the Hells gene, is essential for normal levels of DNA methylation in the mammalian genome. While the role of LSH in the methylation of repetitive DNA sequences is well characterized, its contribution to the regulation of DNA methylation and th...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.108498.110
更新日期:2011-01-01 00:00:00
abstract::Chromosome 21 represents approximately 1% of the human genome, and its long arm has been estimated to contain 600-1000 genes. A dense linkage map and almost complete physical maps based on yeast artificial chromosomes (YACs) and cosmids have been developed. We have used exon trapping to identify portions of genes from...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.6.8.747
更新日期:1996-08-01 00:00:00
abstract::There are numerous examples from the genomes of viruses, mitochondria, and chromosomes that adjacent genes can overlap, sharing at least one nucleotide. Overlaps have been hypothesized to be involved in genome size minimization and as a regulatory mechanism of gene expression. Here we show that overlapping genes are a...
journal_title:Genome research
pub_type: 信件
doi:10.1101/gr.2433104
更新日期:2004-11-01 00:00:00
abstract::Sequencing of the human Y chromosome has uncovered the peculiarities of the genomic organization of a heterogametic sex chromosome of old evolutionary age, and has led to many insights into the evolutionary changes that occurred during its long history. We have studied the genomic organization of the medaka fish Y chr...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.5016106
更新日期:2006-07-01 00:00:00
abstract::Natural killer (NK) cells contribute to the essential functions of innate immunity and reproduction. Various genes encode NK cell receptors that recognize the major histocompatibility complex (MHC) Class I molecules expressed by other cells. For primate NK cells, the killer-cell immunoglobulin-like receptors (KIR) are...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.085738.108
更新日期:2009-05-01 00:00:00
abstract::The expression of most genes is regulated by multiple transcription factors. The interactions between transcription factors produce complex patterns of gene expression that are not always obvious from the arrangement of cis-regulatory elements in a promoter. One critical element of promoters is the TATA box, the docki...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.106732.110
更新日期:2010-10-01 00:00:00
abstract::Cephalochordates, urochordates, and vertebrates evolved from a common ancestor over 520 million years ago. To improve our understanding of chordate evolution and the origin of vertebrates, we intensively searched for particular genes, gene families, and conserved noncoding elements in the sequenced genome of the cepha...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.073676.107
更新日期:2008-07-01 00:00:00
abstract::In comparison to genotypes, knowledge about haplotypes (the combination of alleles present on a single chromosome) is much more useful for whole-genome association studies and for making inferences about human evolutionary history. Haplotypes are typically inferred from population genotype data using computational met...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.077065.108
更新日期:2008-08-01 00:00:00
abstract::Transposable elements (TEs) proliferate within the genome of their host, which responds by silencing them epigenetically. Much is known about the mechanisms of silencing in plants, particularly the role of siRNAs in guiding DNA methylation. In contrast, little is known about siRNA targeting patterns along the length o...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.193763.115
更新日期:2016-02-01 00:00:00
abstract::Little is known about novel genetic elements that drove the emergence of anthropoid primates. We exploited the sequencing of the marmoset genome to identify 23,849 anthropoid-specific constrained (ASC) regions and confirmed their robust functional signatures. Of the ASC base pairs, 99.7% were noncoding, suggesting tha...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.168963.113
更新日期:2014-09-01 00:00:00
abstract::The densities of transposable elements (TEs) in the human genome display substantial variation both within individual chromosomes and among chromosome types (autosomes and the two sex chromosomes). Finding an explanation for this variability has been challenging, especially in light of genome landscapes unique to the ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.099044.109
更新日期:2010-05-01 00:00:00
abstract::Sequence-specific DNA-binding transcription factors have widespread biological significance in the regulation of gene expression. However, in lower prokaryotes and eukaryotic metazoans, it is usually difficult to find transcription regulatory factors that recognize specific target promoters. To address this, we have d...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.086595.108
更新日期:2009-07-01 00:00:00
abstract::The study of genetic variability within natural populations of pathogens may provide insight into their evolution and pathogenesis. We used a Mycobacterium tuberculosis high-density oligonucleotide microarray to detect small-scale genomic deletions among 19 clinically and epidemiologically well-characterized isolates ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.166401
更新日期:2001-04-01 00:00:00
abstract::Plasticity of gene regulatory encryption can permit DNA sequence divergence without loss of function. Functional information is preserved through conservation of the composition of transcription factor binding sites (TFBS) in a regulatory element. We have developed a method that can accurately identify pairs of functi...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.119016.110
更新日期:2011-07-01 00:00:00
abstract::We generated high-resolution maps of histone H3 lysine 9/14 acetylation (H3ac), histone H4 lysine 5/8/12/16 acetylation (H4ac), and histone H3 at lysine 4 mono-, di-, and trimethylation (H3K4me1, H3K4me2, H3K4me3, respectively) across the ENCODE regions. Studying each modification in five human cell lines including th...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.5704207
更新日期:2007-06-01 00:00:00
abstract::DNA transposons, or class 2 transposable elements, have successfully propagated in a wide variety of genomes. However, it is widely believed that DNA transposon activity has ceased in mammalian genomes for at least the last 40 million years. We recently reported evidence for the relatively recent activity of hAT and H...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.071886.107
更新日期:2008-05-01 00:00:00
abstract::We have developed a simplified method for multiplex PCR based on the use of chimeric primers. Each primer contains a 3' region complementary to sequence-specific recognition sites and a 5' region made up of an unrelated 20-nucleotide sequence. Identical reaction conditions, cycling times, and annealing temperatures ha...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.5.5.488
更新日期:1995-12-01 00:00:00
abstract::Mammalian X and Y Chromosomes evolved from an ordinary autosomal pair. Genetic decay of the Y led to X Chromosome inactivation (XCI) in females, but some Y-linked genes were retained during the course of sex chromosome evolution, and many X-linked genes did not become subject to XCI. We reconstructed gene-by-gene dosa...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.230433.117
更新日期:2018-04-01 00:00:00
abstract::Hi-C is a powerful technology for studying genome-wide chromatin interactions. However, current methods for assessing Hi-C data reproducibility can produce misleading results because they ignore spatial features in Hi-C data, such as domain structure and distance dependence. We present HiCRep, a framework for assessin...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.220640.117
更新日期:2017-11-01 00:00:00
abstract::Structured elements of RNA molecules are essential in, e.g., RNA stabilization, localization, and protein interaction, and their conservation across species suggests a common functional role. We computationally screened vertebrate genomes for conserved RNA structures (CRSs), leveraging structure-based, rather than seq...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.208652.116
更新日期:2017-08-01 00:00:00