Abstract：
:The orphan nuclear receptor TLX regulates neural stem cell self-renewal in the adult brain and functions primarily as a transcription repressor through recruitment of Atrophin corepressors, which bind to TLX via a conserved peptide motif termed the Atro box. Here we report crystal structures of the human and insect TLX ligand-binding domain in complex with Atro box peptides. In these structures, TLX adopts an autorepressed conformation in which its helix H12 occupies the coactivator-binding groove. Unexpectedly, H12 in this autorepressed conformation forms a novel binding pocket with residues from helix H3 that accommodates a short helix formed by the conserved ALXXLXXY motif of the Atro box. Mutations that weaken the TLX-Atrophin interaction compromise the repressive activity of TLX, demonstrating that this interaction is required for Atrophin to confer repressor activity to TLX. Moreover, the autorepressed conformation is conserved in the repressor class of orphan nuclear receptors, and mutations of corresponding residues in other members of this class of receptors diminish their repressor activities. Together, our results establish the functional conservation of the autorepressed conformation and define a key sequence motif in the Atro box that is essential for TLX-mediated repression.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Zhi X,Zhou XE,He Y,Searose-Xu K,Zhang CL,Tsai CC,Melcher K,Xu HEdoi
10.1101/gad.254904.114subject
Has Abstractpub_date
2015-02-15 00:00:00pages
440-50issue
4eissn
0890-9369issn
1549-5477pii
29/4/440journal_volume
29pub_type
杂志文章abstract：:The histone variants H3.3 and H2A.Z have recently emerged as two of the most important features in transcriptional regulation, the molecular mechanism of which still remains poorly understood. In this study, we investigated the regulation of H3.3 and H2A.Z on chromatin dynamics during transcriptional activation. Our i...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.222174.113
更新日期：2013-10-01 00:00:00
abstract：:Specific recognition of splice sites within metazoan mRNA precursors (pre-mRNAs) is a potential stage for gene regulation by alternative splicing. Splicing factors of the SR protein family play a major role in this regulation, as they are required for early recognition of splice sites during spliceosome assembly. Here...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.13.6.740
更新日期：1999-03-15 00:00:00
abstract：:To investigate the importance of sequences between the yeast (Saccharomyces cerevisiae) branch point (TACTAAC box) and 3' splice site (AG), we generated a series of pre-mRNA substrates that differed in the length of RNA retained on the 3' side of the TACTAAC box. These pre-mRNAs were compared as substrates for the fir...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1.3.238
更新日期：1987-05-01 00:00:00
abstract：:Cap-dependent translation is mediated by eIF4F, a protein complex composed of three subunits as follows: eIF4E, which recognizes the mRNA 5' cap structure; eIF4A, an RNA-helicase; and eIF4G, a scaffolding protein that binds eIF4E, eIF4A, and the eIF4E-kinase Mnk1 simultaneously. eIF4E is hypophosphorylated and cap-dep...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.889201
更新日期：2001-08-15 00:00:00
abstract：:The oncoprotein MDM2 binds to the activation domain of the tumor suppressor p53 and inhibits its ability to stimulate transcription. This same region of p53 is able to bind several basal transcription factors that appear to be important for the transactivation function of p53. It has therefore been suggested that MDM2...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.11.15.1974
更新日期：1997-08-01 00:00:00
abstract：:Gut homeostasis is controlled by both immune and developmental mechanisms, and its disruption can lead to inflammatory disorders or cancerous lesions of the intestine. While the impact of bacteria on the mucosal immune system is beginning to be precisely understood, little is known about the effects of bacteria on gut...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1827009
更新日期：2009-10-01 00:00:00
abstract：:Dosage compensation is a process required to balance the expression of X-linked genes between males and females. In Drosophila this is achieved by targeting the dosage compensation complex or the male-specific lethal (MSL) complex to the male X chromosome. In order to study the mechanism of targeting, we have studied ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.430807
更新日期：2007-08-15 00:00:00
abstract：:The amyloid precursor protein (APP) has garnered considerable attention due to its genetic links to Alzheimer's disease. Death receptor 6 (DR6) was recently shown to bind APP via the protein extracellular regions, stimulate axonal pruning, and inhibit synapse formation. Here, we report the crystal structure of the DR6...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.257675.114
更新日期：2015-04-15 00:00:00
abstract：:Recombination catalyzed by the Flp site-specific recombinase involves breakage and joining of four DNA strands between two target substrates. The reaction is carried out in two steps of pairwise strand exchanges by a DNA-protein assembly in which four Flp monomers act cooperatively to execute strand cleavage and joini...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.11.18.2438
更新日期：1997-09-15 00:00:00
abstract：:Smads regulate transcription of defined genes in response to TGF-beta receptor activation, although the mechanisms of Smad-mediated transcription are not well understood. We demonstrate that the TGF-beta-inducible Smad3 uses the tumor suppressor Smad4/DPC4 and CBP/p300 as transcriptional coactivators, which associate ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.12.14.2153
更新日期：1998-07-15 00:00:00
abstract：:Small cell lung cancer (SCLC) is an aggressive neuroendocrine cancer characterized by initial chemosensitivity followed by emergence of chemoresistant disease. To study roles for MYCN amplification in SCLC progression and chemoresistance, we developed a genetically engineered mouse model of MYCN-overexpressing SCLC. I...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.340133.120
更新日期：2020-09-01 00:00:00
abstract：:Adult mesenchymal stem cells (MSCs) derived from bone marrow contribute to the regeneration of multiple types of mesenchymal tissues. Here we describe the functional role of a novel form of cross-talk between the transforming growth factor beta1 (TGF-beta1) and Wnt signaling pathways in regulating the activities of hu...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1388806
更新日期：2006-03-15 00:00:00
abstract：:The target gene(s) required for Myc-mediated tumorigenesis are still elusive. Here we show that while endogenous c-Myc is surprisingly dispensable for skin homeostasis and TPA-induced hyperplasia, c-Myc-deficient epidermis is resistant to Ras-mediated DMBA/TPAinduced tumorigenesis. This is mechanistically linked to p2...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.381206
更新日期：2006-08-01 00:00:00
abstract：:To understand the organization of the transcriptional networks that govern cell differentiation, we have investigated the transcriptional circuitry controlling pseudohyphal development in Saccharomyces cerevisiae. The binding targets of Ste12, Tec1, Sok2, Phd1, Mga1, and Flo8 were globally mapped across the yeast geno...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1389306
更新日期：2006-02-15 00:00:00
abstract：:IkappaB kinases (IKKs) IKK1 and IKK2 are two putative IkappaBalpha kinases involved in NF-kappaB activation. To examine the in vivo functions of IKK1, we generated IKK1-deficient mice. The mutant mice are perinatally lethal and exhibit a wide range of developmental defects. Newborn mutant mice have shiny, taut, and st...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.13.10.1322
更新日期：1999-05-15 00:00:00
abstract：:Faithful inheritance of genetic information requires that DNA be copied only once each cell cycle. Initiation of DNA replication involves the establishment of a prereplication complex (pre-RC) and subsequent activation by CDK/cyclins, converting the pre-RC to a post-RC. The origin recognition complex (ORC), Cdc6p, and...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.11.24.3375
更新日期：1997-12-15 00:00:00
abstract：:The repression of the maternally inherited Igf2 allele has been proposed to depend on a methylation-sensitive chromatin insulator organized by the 11 zinc finger protein CTCF at the H19 imprinting control region (ICR). Here we document that point mutations of the nucleotides in physical contact with CTCF within the en...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.254903
更新日期：2003-03-01 00:00:00
abstract：:In Saccharomyces cerevisiae, short noncoding RNA (ncRNA) generated by RNA polymerase II (Pol II) are terminated by the NRD complex consisting of Nrd1, Nab3, and Sen1. We now show that Pcf11, a component of the cleavage and polyadenylation complex (CPAC), is also generally required for NRD-dependent transcription termi...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.251470.114
更新日期：2015-04-15 00:00:00
abstract：:A relevant, yet little recognized feature of antisense regulation is the possibility of switching roles between regulatory and regulated RNAs. Here we show that induction of a Salmonella gene relies on the conversion of a small RNA from effector to regulatory target. The chiP gene (formerly ybfM), identified and chara...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.541609
更新日期：2009-09-01 00:00:00
abstract：:The senescence-associated secretory phenotype (SASP) is a major trait of senescent cells, but the molecular regulators of SASP factor secretion are poorly understood. Mass spectrometry analysis revealed that secretory carrier membrane protein 4 (SCAMP4) levels were strikingly elevated on the surface of senescent cells...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.313270.118
更新日期：2018-07-01 00:00:00
abstract：:Developmental responses to the plant hormone auxin are thought to be mediated by interacting pairs from two protein families: short-lived inhibitory IAA proteins and ARF transcription factors binding to auxin-response elements. monopteros mutants lacking activating ARF5 and the auxin-insensitive mutant bodenlos fail t...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.229402
更新日期：2002-07-01 00:00:00
abstract：:Sequence-specific DNA-binding activators, key regulators of gene expression, stimulate transcription in part by targeting the core promoter recognition TFIID complex and aiding in its recruitment to promoter DNA. Although it has been established that activators can interact with multiple components of TFIID, it is unk...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1790709
更新日期：2009-07-01 00:00:00
abstract：:Signals from TGF-beta superfamily receptors are transduced to the nucleus by Smad proteins, which transcriptionally activate target genes. In Caenorhabditis elegans, defects in a TGF-beta-related pathway cause a reversible developmental arrest and metabolic shift at the dauer larval stage. Null mutations in daf-3 supp...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.11.20.2679
更新日期：1997-10-15 00:00:00
abstract：:rhomboid (rho) belongs to a group of four genes involved in the elaboration of positional information at a ventrolateral level in the Drosophila embryo. Mutations at any of these four loci also lead to a variety of other phenotypes, including reduction in the number of stretch receptor organs (chordotonal organs) in t...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.4.2.190
更新日期：1990-02-01 00:00:00
abstract：:The 134-bp enhancer region of the pancreatic elastase I gene is sufficient to direct pancreatic acinar cell-specific transcription in transgenic mice and in transfected cells in culture. Ten-base-pair scanner mutations in three separate enhancer domains that inactivate enhancer function in transfected pancreatic cells...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.3.5.687
更新日期：1989-05-01 00:00:00
abstract：:The yeast HO gene is transcribed transiently during G1 as cells undergo START. START-specific HO activation requires two proteins, SWI4 and SWI6, which act via a motif (CACGA4) repeated up to 10 times within the URS2 region of the HO promoter. We identified a DNA-binding activity containing SWI4 and SWI6 that recogniz...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.5.11.2000
更新日期：1991-11-01 00:00:00
abstract：:In many species, a dosage compensation complex (DCC) is targeted to X chromosomes of one sex to equalize levels of X-gene products between males (1X) and females (2X). Here we identify cis-acting regulatory elements that target the Caenorhabditis elegans X chromosome for repression by the DCC. The DCC binds to discret...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1751109
更新日期：2009-03-01 00:00:00
abstract：:The yeast SAGA (Spt-Ada-Gcn5-acetyltransferase) coactivator complex exerts functions in gene expression, including activator interaction, histone acetylation, histone deubiquitination, mRNA export, chromatin recognition, and regulation of the basal transcription machinery. These diverse functions involve distinct modu...
journal_title：Genes & development
pub_type： 杂志文章,评审
doi：10.1101/gad.184705.111
更新日期：2012-03-15 00:00:00
abstract：:Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the United States with a median survival of <6 mo and a dismal 5-yr survival rate of 3%-5%. The cancer's lethal nature stems from its propensity to rapidly disseminate to the lymphatic system and distant organs. This aggressive biol...
journal_title：Genes & development
pub_type： 杂志文章,评审
doi：10.1101/gad.1415606
更新日期：2006-05-15 00:00:00
abstract：:The X-inactive-specific transcript (Xist) locus is a cis-acting switch that regulates X chromosome inactivation in mammals. Over recent years an important goal has been to understand how Xist is regulated at the initiation of X inactivation. Here we report the analysis of a series of targeted mutations at the 5' end o...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.271203
更新日期：2003-09-01 00:00:00
