Abstract:
:Sonic hedgehog (Shh) signals via Gli transcription factors to direct digit number and identity in the vertebrate limb. We characterized the Gli-dependent cis-regulatory network through a combination of whole-genome chromatin immunoprecipitation (ChIP)-on-chip and transcriptional profiling of the developing mouse limb. These analyses identified approximately 5000 high-quality Gli3-binding sites, including all known Gli-dependent enhancers. Discrete binding regions exhibit a higher-order clustering, highlighting the complexity of cis-regulatory interactions. Further, Gli3 binds inertly to previously identified neural-specific Gli enhancers, demonstrating the accessibility of their cis-regulatory elements. Intersection of DNA binding data with gene expression profiles predicted 205 putative limb target genes. A subset of putative cis-regulatory regions were analyzed in transgenic embryos, establishing Blimp1 as a direct Gli target and identifying Gli activator signaling in a direct, long-range regulation of the BMP antagonist Gremlin. In contrast, a long-range silencer cassette downstream from Hand2 likely mediates Gli3 repression in the anterior limb. These studies provide the first comprehensive characterization of the transcriptional output of a Shh-patterning process in the mammalian embryo and a framework for elaborating regulatory networks in the developing limb.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Vokes SA,Ji H,Wong WH,McMahon APdoi
10.1101/gad.1693008subject
Has Abstractpub_date
2008-10-01 00:00:00pages
2651-63issue
19eissn
0890-9369issn
1549-5477pii
22/19/2651journal_volume
22pub_type
杂志文章abstract::The gene for an essential protein subunit of nuclear RNase P from Saccharomyces cerevisiae has been cloned. The gene for this protein, RPP1, was identified by virtue of its homology with a human scleroderma autoimmune antigen, Rpp30, which copurifies with human RNase P. Epitope-tagged Rpp1 can be found in association ...
journal_title:Genes & development
pub_type: 更正并重新发布的文章,杂志文章
doi:10.1101/gad.11.21.2926
更新日期:1997-11-01 00:00:00
abstract::The histone regulatory (HIR) and histone promoter control (HPC) repressor proteins regulate three of the four histone gene loci during the Saccharomyces cerevisiae cell cycle. Here, we demonstrate that Hir1, Hir2, Hir3, and Hpc2 proteins form a stable HIR repressor complex. The HIR complex promotes histone deposition ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1341105
更新日期:2005-11-01 00:00:00
abstract::The td, nrdB, and sunY introns of bacteriophage T4 each contain a long open reading frame (ORF). These ORFs are preceded by functional T4 late promoters and, in the case of the nrdB intron ORF, a functional middle promoter. Expression of phage-encoded intron ORF-lacZ fusions indicates that these T4 genes are highly re...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.12b.1791
更新日期:1988-12-01 00:00:00
abstract::Bone morphogenic proteins 2 and 4 (BMP2 and BMP4) inhibit proliferation and induce differentiation of cerebellar granule neuron progenitors (GNPs) and primary GNP-like medulloblastoma (MB) cells. This occurs through rapid proteasome-mediated degradation of Math1 (Atoh1), a transcription factor expressed in proliferati...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1636408
更新日期:2008-03-15 00:00:00
abstract::The ultraviolet (UV)-induced (6-4) pyrimidine-pyrimidone photoproduct [(6-4) PP] confers a large structural distortion in DNA. Here we examine in human cells the roles of translesion synthesis (TLS) DNA polymerases (Pols) in promoting replication through a (6-4) TT photoproduct carried on a duplex plasmid where bidire...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1872810
更新日期:2010-01-15 00:00:00
abstract::Subependymal nodules (SENs) and subependymal giant cell astrocytomas (SEGAs) are common brain lesions found in patients with tuberous sclerosis complex (TSC). These brain lesions present a mixed glioneuronal phenotype and have been hypothesized to originate from neural stem cells. However, this hypothesis has not been...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.16750211
更新日期:2011-08-01 00:00:00
abstract::Translation of encephalomyocarditis virus (EMCV) mRNA occurs by ribosomal internal entry into the 5'-nontranslated region (5' NTR) rather than by ribosomal scanning. The internal ribosomal entry site (IRES) in the EMCV 5' NTR was determined by in vitro translation with RNAs that were generated by in vitro transcriptio...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.9.1560
更新日期:1990-09-01 00:00:00
abstract::Nonsense-mediated decay (NMD) is a translation-dependent RNA quality control mechanism that occurs in the cytoplasm. However, it is unknown how NMD regulates the stability of RNAs translated at the endoplasmic reticulum (ER). Here, we identify a localized NMD pathway dedicated to ER-translated mRNAs. We previously ide...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.338061.120
更新日期:2020-08-01 00:00:00
abstract::We characterized a gene, extradenticle, which seems to interact with a specific subset of Drosophila homeo domain proteins, possibly affecting their target specificity. This interpretation is based on an examination of the zygotic and maternal effect phenotypes of extradenticle mutations. In embryos with reduced level...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.7.1209
更新日期:1990-07-01 00:00:00
abstract::Histone post-translational modifications regulate chromatin structure and function largely through interactions with effector proteins that often contain multiple histone-binding domains. While significant progress has been made characterizing individual effector domains, the role of paired domains and how they functi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.220467.113
更新日期:2013-06-01 00:00:00
abstract::Bardet-Biedl syndrome (BBS) is a genetically heterogeneous developmental disorder whose molecular basis is largely unknown. Here, we show that mutations in the Caenorhabditis elegans bbs-7 and bbs-8 genes cause structural and functional defects in cilia. C. elegans BBS proteins localize predominantly at the base of ci...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1194004
更新日期:2004-07-01 00:00:00
abstract::The YAP transcription coactivator has been implicated as an oncogene and is amplified in human cancers. Recent studies have established that YAP is phosphorylated and inhibited by the Hippo tumor suppressor pathway. Here we demonstrate that the TEAD family transcription factors are essential in mediating YAP-dependent...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1664408
更新日期:2008-07-15 00:00:00
abstract::Class Ia phosphatidylinositol 3 kinase (PI3K) is required for oncogenic receptor-mediated transformation; however, the individual roles of the two commonly expressed class Ia PI3K isoforms in oncogenic receptor signaling have not been elucidated in vivo. Here, we show that genetic ablation of p110α blocks tumor format...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.191973.112
更新日期:2012-07-15 00:00:00
abstract::Cohesin is a chromosome-associated multisubunit protein complex that is highly conserved in eukaryotes and has close homologs in bacteria. Cohesin mediates cohesion between replicated sister chromatids and is therefore essential for chromosome segregation in dividing cells. Cohesin is also required for efficient repai...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1724308
更新日期:2008-11-15 00:00:00
abstract::To investigate the relationship between splicing and polyadenylation during the production of vertebrate mRNAs, we examined the effect of mutation of a poly(A) site on splicing of upstream introns. Mutation of the AAUAAA polyadenylation consensus sequence inhibited in vitro splicing of an upstream intron. The magnitud...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.11.2086
更新日期:1991-11-01 00:00:00
abstract::To determine whether 9-cis retinoic acid receptors (RXRs) regulate the biological activity of all-trans retinoic acid (tRA) and its receptors (RARs) in skin, we have targeted a dominant-negative RXR alpha (dnRXR alpha) lacking transactivation function AF-2 to differentiated suprabasal keratinocytes in the epidermis of...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.1.59
更新日期:1997-01-01 00:00:00
abstract::Hundreds of microRNAs (miRNAs) have been discovered in metazoans and plants, and understanding of their biogenesis has advanced dramatically; however, relatively little is known about the cofactors necessary for miRNA regulation of target gene expression. In Caenorhabditis elegans, the conserved miRNA let-7 and its pa...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.17153811
更新日期:2011-10-01 00:00:00
abstract::To determine the prevalence of cotranscriptional splicing in Drosophila, we sequenced nascent RNA transcripts from Drosophila S2 cells as well as from Drosophila heads. Eighty-seven percent of the introns assayed manifest >50% cotranscriptional splicing. The remaining 13% are cotranscriptionally spliced poorly or slow...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.178962.111
更新日期:2011-12-01 00:00:00
abstract::The sigma(28) protein is a member of the bacterial sigma(70)-family of transcription factors that directs RNA polymerase to flagellar late (class 3) promoters. The sigma(28) protein is regulated in response to flagellar assembly by the anti-sigma(28) factor FlgM. FlgM inhibits sigma(28)-dependent transcription of gene...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.380406
更新日期:2006-08-15 00:00:00
abstract::A key pathway that controls both cell division and differentiation in animal cells is mediated by the retinoblastoma (RB) family of tumor suppressors, which gate the passage of cells from G(1) to S and through S phase. The role(s) of the RB pathway in plants are not yet clearly defined, nor has there been any evidence...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.892101
更新日期:2001-07-01 00:00:00
abstract::Cosuppression is a silencing phenomenon triggered by the introduction of homologous DNA sequences into the genomes of organisms as diverse as plants, fungi, flies, and nematodes. Here we report sex-induced silencing (SIS), which is triggered by tandem integration of a transgene array in the human fungal pathogen Crypt...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1970910
更新日期:2010-11-15 00:00:00
abstract::Keratinocyte growth factor (KGF), also known as fibroblast growth factor 7 (FGF7), is synthesized by skin fibroblasts. However, its mitogenic activity is on skin keratinocytes, where it is the most potent growth factor identified thus far. To explore KGF's function in vivo, we used embryonic stem cell technology to ge...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.2.165
更新日期:1996-01-15 00:00:00
abstract::Mammalian cells exhibit a complex response to DNA damage. The tumor suppressor BRCA1 and associated protein BARD1 are thought to play an important role in this response, and our previous work demonstrated that this includes transient inhibition of the pre-mRNA 3' processing machinery. Here we provide evidence that thi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1309505
更新日期:2005-05-15 00:00:00
abstract::The enzyme telomerase, which elongates chromosome termini, is a critical factor in determining long-term cellular proliferation and tissue renewal. Hence, even small differences in telomerase levels can have substantial consequences for human health. In budding yeast, telomerase consists of the catalytic Est2 protein ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.246256.114
更新日期:2014-10-01 00:00:00
abstract::Here we show that the cell cycle defects of dE2F1-depleted cells depend on the cooperative effects of dE2F2 and DACAPO (DAP), an inhibitor of Cyclin E/cyclin-dependent kinase 2 (CycE/cdk2). The different properties of cells lacking dE2F1/dE2F2 and dE2F1/DAP lead to the surprising observation that dE2F2-mediated repres...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1031803
更新日期:2003-03-15 00:00:00
abstract::Long understood as a bona fide tumor suppressor that safeguards the integrity of the genome via regulating numerous cellular outcomes, p53 may also exert its decisive and versatile functions by controlling DNA methylation. In this issue of Genes & Development, Tovy and colleagues (pp. 959-972) report that, in naïve mo...
journal_title:Genes & development
pub_type: 评论,杂志文章,评审
doi:10.1101/gad.302364.117
更新日期:2017-05-15 00:00:00
abstract::We have cloned four cyclin-B homologs from Saccharomyces cerevisiae, CLB1-CLB4, using the polymerase chain reaction and low stringency hybridization approaches. These genes form two classes based on sequence relatedness: CLB1 and CLB2 show highest homology to the Schizosaccharomyces pombe cyclin-B homolog cdc13 involv...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.11.2021
更新日期:1992-11-01 00:00:00
abstract::In petunia flowers, the loci an1, an2, and an11 control the pigmentation of the flower by stimulating the transcription of anthocyanin biosynthetic genes. The an1 and an2 locus were recently cloned and encode a basic helix-loop-helix (bHLH) and MYB-domain transcriptional activator, respectively. Here, we report the is...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.11.1422
更新日期:1997-06-01 00:00:00
abstract::The Neurospora crassa clock-controlled gene (ccg-2) is transcriptionally activated by the circadian clock in a time-of-day-specific manner. Transcript and sequence analyses of ccg-2 reveal that the predicted Ccg-2 polypeptide bears significant similarity to a class of low-molecular-weight, cysteine-rich, hydrophobic p...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.12a.2382
更新日期:1992-12-01 00:00:00
abstract::The mammalian high mobility group proteins HMG1 and HMG2 are abundant, chromatin-associated proteins whose cellular function is not known. In this study we show that these proteins can substitute for the prokaryotic DNA-bending protein HU in promoting the assembly of the Hin invertasome, an intermediate structure in H...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.8.1521
更新日期:1993-08-01 00:00:00