Skewing X chromosome choice by modulating sense transcription across the Xist locus.

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 of the Xist locus. A number of these mutations were found to cause preferential inactivation, to varying degrees, of the X chromosome bearing the targeted allele in XX heterozygotes. This phenotype is similar to that seen with mutations that ablate Tsix, an antisense RNA initiated 3' of Xist. Interestingly, each of the 5' mutations causing nonrandom X inactivation was found to exhibit ectopic sense transcription in embryonic stem (ES) cells. The level of ectopic transcription was seen to correlate with the degree of X inactivation skewing. Conversely, targeted mutations which did not affect randomness of X inactivation also did not exhibit ectopic sense transcription. These results indicate that X chromosome choice is determined by the balance of Xist sense and antisense transcription prior to the onset of random X inactivation.

journal_name

Genes Dev

journal_title

Genes & development

authors

Nesterova TB,Johnston CM,Appanah R,Newall AE,Godwin J,Alexiou M,Brockdorff N

doi

10.1101/gad.271203

subject

Has Abstract

pub_date

2003-09-01 00:00:00

pages

2177-90

issue

17

eissn

0890-9369

issn

1549-5477

pii

17/17/2177

journal_volume

17

pub_type

杂志文章
  • Role of DNA damage-induced replication checkpoint in promoting lesion bypass by translesion synthesis in yeast.

    abstract::Unrepaired DNA lesions in the template strand block the replication fork. In yeast, Mec1 protein kinase-mediated replication checkpoint prevents the breakdown of replication forks and maintains viability in DNA-damaged cells going through the S phase. By ensuring that the replisome does not dissociate from the fork st...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1793409

    authors: Pagès V,Santa Maria SR,Prakash L,Prakash S

    更新日期:2009-06-15 00:00:00

  • Tight protein-DNA interactions favor gene silencing.

    abstract::The heterochromatin-like structure formed by the yeast silent information regulator complex (SIR) represses transcription at the silent mating type loci and telomeres. Here, we report that tight protein-DNA complexes induce ectopic recruitment of the SIR complex, promoting gene silencing and changes in subnuclear loca...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.611011

    authors: Dubarry M,Loïodice I,Chen CL,Thermes C,Taddei A

    更新日期:2011-07-01 00:00:00

  • Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense.

    abstract::Macrophage activation by the proinflammatory cytokine interferon-gamma (IFN-gamma) is a critical component of the host innate response to bacterial pathogenesis. However, the precise nature of the IFN-gamma-induced activation pathway is not known. Here we show using genome-wide expression and chromatin-binding profili...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1553007

    authors: Sonoda J,Laganière J,Mehl IR,Barish GD,Chong LW,Li X,Scheffler IE,Mock DC,Bataille AR,Robert F,Lee CH,Giguère V,Evans RM

    更新日期:2007-08-01 00:00:00

  • Addicted to Myc--but why?

    abstract::Many tumors continuously depend on the initiating oncogenes, but whether this extends to their downstream targets is unclear. In this issue of Genes & Development, Sodir and colleagues (pp. 907-916) demonstrate an essential role for endogenous Myc proteins in maintaining the tumor microenvironment, providing an unexpe...

    journal_title:Genes & development

    pub_type: 评论,杂志文章

    doi:10.1101/gad.2053311

    authors: von Eyss B,Eilers M

    更新日期:2011-05-01 00:00:00

  • Protein kinase A antagonizes Hedgehog signaling by regulating both the activator and repressor forms of Cubitus interruptus.

    abstract::The Hedgehog (Hh) family of secreted proteins controls many aspects of animal development. In Drosophila, Hh transduces its signal via Cubitus interruptus (Ci), a transcription factor present in two forms: a full-length activator and a carboxy-terminally truncated repressor that is derived from the full-length form by...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.13.21.2828

    authors: Wang G,Wang B,Jiang J

    更新日期:1999-11-01 00:00:00

  • SUMO-targeted ubiquitin E3 ligase RNF4 is required for the response of human cells to DNA damage.

    abstract::Here we demonstrate that RNF4, a highly conserved small ubiquitin-like modifier (SUMO)-targeted ubiquitin E3 ligase, plays a critical role in the response of mammalian cells to DNA damage. Human cells in which RNF4 expression was ablated by siRNA or chicken DT40 cells with a homozygous deletion of the RNF4 gene displa...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.189274.112

    authors: Yin Y,Seifert A,Chua JS,Maure JF,Golebiowski F,Hay RT

    更新日期:2012-06-01 00:00:00

  • Conversion of a gene-specific repressor to a regional silencer.

    abstract::In Saccharomyces cerevisiae, gene silencing at the HMR and HML loci is normally dependent on Sir2p, Sir3p, and Sir4p, which are structural components of silenced chromatin. Sir2p is a NAD+-dependent histone deacetylase required for silencing. Silencing can be restored in cells lacking Sir proteins by a dominant mutati...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.873601

    authors: Rusché LN,Rine J

    更新日期:2001-04-15 00:00:00

  • A condensin-like dosage compensation complex acts at a distance to control expression throughout the genome.

    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

    authors: Jans J,Gladden JM,Ralston EJ,Pickle CS,Michel AH,Pferdehirt RR,Eisen MB,Meyer BJ

    更新日期:2009-03-01 00:00:00

  • Genetics of dark skin in mice.

    abstract::Chemical mutagenesis in the mouse is a powerful approach for phenotype-driven genetics, but questions remain about the efficiency with which new mutations ascertained by their phenotype can be localized and identified, and that knowledge applied to a specific biological problem. During a global screen for dominant phe...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1023703

    authors: Fitch KR,McGowan KA,van Raamsdonk CD,Fuchs H,Lee D,Puech A,Hérault Y,Threadgill DW,Hrabé de Angelis M,Barsh GS

    更新日期:2003-01-15 00:00:00

  • Circular forms of developmentally excised DNA in Euplotes crassus have a heteroduplex junction.

    abstract::Extensive DNA elimination via a DNA breakage and rejoining process occurs during macronuclear development in the hypotrich ciliate Euplotes crassus. The excision process involves the removal of short, unique segments of DNA (internal eliminated sequences; IESs) and at least two highly repetitive families of transposon...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.7.1.84

    authors: Klobutcher LA,Turner LR,LaPlante J

    更新日期:1993-01-01 00:00:00

  • The scaffold protein WRAP53β orchestrates the ubiquitin response critical for DNA double-strand break repair.

    abstract::The WD40 domain-containing protein WRAP53β (WD40 encoding RNA antisense to p53; also referred to as WDR79/TCAB1) controls trafficking of splicing factors and the telomerase enzyme to Cajal bodies, and its functional loss has been linked to carcinogenesis, premature aging, and neurodegeneration. Here, we identify WRAP5...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.246546.114

    authors: Henriksson S,Rassoolzadeh H,Hedström E,Coucoravas C,Julner A,Goldstein M,Imreh G,Zhivotovsky B,Kastan MB,Helleday T,Farnebo M

    更新日期:2014-12-15 00:00:00

  • A genome-wide RNAi screen identifies multiple RSK-dependent regulators of cell migration.

    abstract::To define the functional pathways regulating epithelial cell migration, we performed a genome-wide RNAi screen using 55,000 pooled lentiviral shRNAs targeting ∼11,000 genes, selecting for transduced cells with increased motility. A stringent validation protocol generated a set of 31 genes representing diverse pathways...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1989110

    authors: Smolen GA,Zhang J,Zubrowski MJ,Edelman EJ,Luo B,Yu M,Ng LW,Scherber CM,Schott BJ,Ramaswamy S,Irimia D,Root DE,Haber DA

    更新日期:2010-12-01 00:00:00

  • Sonic hedgehog acts cell-autonomously on muscle precursor cells to generate limb muscle diversity.

    abstract::How muscle diversity is generated in the vertebrate body is poorly understood. In the limb, dorsal and ventral muscle masses constitute the first myogenic diversification, as each gives rise to distinct muscles. Myogenesis initiates after muscle precursor cells (MPCs) have migrated from the somites to the limb bud and...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.187807.112

    authors: Anderson C,Williams VC,Moyon B,Daubas P,Tajbakhsh S,Buckingham ME,Shiroishi T,Hughes SM,Borycki AG

    更新日期:2012-09-15 00:00:00

  • Enzymatic regulation of pattern: BMP4 binds CUB domains of Tolloids and inhibits proteinase activity.

    abstract::In Xenopus embryos, a dorsal-ventral patterning gradient is generated by diffusing Chordin/bone morphogenetic protein (BMP) complexes cleaved by BMP1/Tolloid metalloproteinases in the ventral side. We developed a new BMP1/Tolloid assay using a fluorogenic Chordin peptide substrate and identified an unexpected negative...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1839309

    authors: Lee HX,Mendes FA,Plouhinec JL,De Robertis EM

    更新日期:2009-11-01 00:00:00

  • DOT1L regulates dystrophin expression and is critical for cardiac function.

    abstract::Histone methylation plays an important role in regulating gene expression. One such methylation occurs at Lys 79 of histone H3 (H3K79) and is catalyzed by the yeast DOT1 (disruptor of telomeric silencing) and its mammalian homolog, DOT1L. Previous studies have demonstrated that germline disruption of Dot1L in mice res...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.2018511

    authors: Nguyen AT,Xiao B,Neppl RL,Kallin EM,Li J,Chen T,Wang DZ,Xiao X,Zhang Y

    更新日期:2011-02-01 00:00:00

  • A unified allosteric/torpedo mechanism for transcriptional termination on human protein-coding genes.

    abstract::The allosteric and torpedo models have been used for 30 yr to explain how transcription terminates on protein-coding genes. The former invokes termination via conformational changes in the transcription complex and the latter proposes that degradation of the downstream product of poly(A) signal (PAS) processing is imp...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.332833.119

    authors: Eaton JD,Francis L,Davidson L,West S

    更新日期:2020-01-01 00:00:00

  • Genome-wide analyses identify transcription factors required for proper morphogenesis of Drosophila sensory neuron dendrites.

    abstract::Dendrite arborization patterns are critical determinants of neuronal function. To explore the basis of transcriptional regulation in dendrite pattern formation, we used RNA interference (RNAi) to screen 730 transcriptional regulators and identified 78 genes involved in patterning the stereotyped dendritic arbors of cl...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1391006

    authors: Parrish JZ,Kim MD,Jan LY,Jan YN

    更新日期:2006-04-01 00:00:00

  • ELAV inhibits 3'-end processing to promote neural splicing of ewg pre-mRNA.

    abstract::The embryonic lethal abnormal visual system (ELAV) is a gene-specific regulator of alternative pre-mRNA processing in neurons of Drosophila. Here we define a functional in vivo binding site for ELAV in neurons through the development of a reporter gene system in transgenic animals in combination with in vitro binding ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1106703

    authors: Soller M,White K

    更新日期:2003-10-15 00:00:00

  • Not just scaffolding: plectin regulates actin dynamics in cultured cells.

    abstract::Plectin, a major linker and scaffolding protein of the cytoskeleton, has been shown to be essential for the mechanical integrity of skin, skeletal muscle, and heart. Studying fibroblast and astroglial cell cultures derived from plectin (-/-) mice, we found that their actin cytoskeleton, including focal adhesion contac...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.12.21.3442

    authors: Andrä K,Nikolic B,Stöcher M,Drenckhahn D,Wiche G

    更新日期:1998-11-01 00:00:00

  • New POU dimer configuration mediates antagonistic control of an osteopontin preimplantation enhancer by Oct-4 and Sox-2.

    abstract::The POU transcription factor Oct-4 is expressed specifically in the germ line, pluripotent cells of the pregastrulation embryo and stem cell lines derived from the early embryo. Osteopontin (OPN) is a protein secreted by cells of the preimplantation embryo and contains a GRGDS motif that can bind to specific integrin ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.12.13.2073

    authors: Botquin V,Hess H,Fuhrmann G,Anastassiadis C,Gross MK,Vriend G,Schöler HR

    更新日期:1998-07-01 00:00:00

  • The Stat6-regulated KRAB domain zinc finger protein Zfp157 regulates the balance of lineages in mammary glands and compensates for loss of Gata-3.

    abstract::Lineage commitment studies in mammary glands have focused on identifying cell populations that display stem or progenitor properties. However, the mechanisms that control cell fate have been incompletely explored. Herein we show that zinc finger protein 157 (Zfp157) is required to establish the balance between luminal...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.184051.111

    authors: Oliver CH,Khaled WT,Frend H,Nichols J,Watson CJ

    更新日期:2012-05-15 00:00:00

  • A two-base change in a POU factor-binding site switches pituitary-specific to lymphoid-specific gene expression.

    abstract::The structurally related POU homeo domain proteins Pit-1 and Oct-2 activate pituitary- and lymphoid-specific transcription, respectively, by binding to similar AT-rich motifs in their target genes. In this study we identify bases critical for recognition and activation by Pit-1 and examine how small differences in Pit...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.4.1.43

    authors: Elsholtz HP,Albert VR,Treacy MN,Rosenfeld MG

    更新日期:1990-01-01 00:00:00

  • Mismatch repair-dependent processing of methylation damage gives rise to persistent single-stranded gaps in newly replicated DNA.

    abstract::O(6)-Methylguanine ((Me)G) is a highly cytotoxic DNA modification generated by S(N)1-type methylating agents. Despite numerous studies implicating DNA replication, mismatch repair (MMR), and homologous recombination (HR) in (Me)G toxicity, its mode of action has remained elusive. We studied the molecular transactions ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.455407

    authors: Mojas N,Lopes M,Jiricny J

    更新日期:2007-12-15 00:00:00

  • A protein that shuttles between the nucleus and the cytoplasm is an important mediator of RNA export.

    abstract::The connection between RNA and protein export from the nucleus was examined in the budding yeast Saccharomyces cerevisiae. NPL3 encodes an RNA-binding protein that shuttles in and out of the nucleus. Export of poly(A)+ RNA has been shown previously to be blocked in np13-1 mutants. To understand the role of Np13p in RN...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.10.10.1233

    authors: Lee MS,Henry M,Silver PA

    更新日期:1996-05-15 00:00:00

  • Nascent peptide-mediated translation elongation arrest coupled with mRNA degradation in the CGS1 gene of Arabidopsis.

    abstract::Expression of the Arabidopsis CGS1 gene that codes for cystathionine gamma-synthase is feedback regulated at the step of mRNA stability in response to S-adenosyl-L-methionine (AdoMet). A short stretch of amino acid sequence, called the MTO1 region, encoded by the first exon of CGS1 itself is involved in this regulatio...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1317105

    authors: Onouchi H,Nagami Y,Haraguchi Y,Nakamoto M,Nishimura Y,Sakurai R,Nagao N,Kawasaki D,Kadokura Y,Naito S

    更新日期:2005-08-01 00:00:00

  • Transcription factor CREM coordinates the timing of hepatocyte proliferation in the regenerating liver.

    abstract::The liver regenerates upon partial hepatectomy (PH) as terminally differentiated hepatocytes undergo a tremendous proliferative process. CREM gene expression is powerfully induced during liver regeneration. We show that cell proliferation is significantly reduced upon PH in CREM-/- mice. There is a reduction in DNA sy...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.12.23.3639

    authors: Servillo G,Della Fazia MA,Sassone-Corsi P

    更新日期:1998-12-01 00:00:00

  • Mouse models for human lung cancer.

    abstract::In recent years several new mouse models for lung cancer have been described. These include models for both non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Tumorigenesis in these conditional mouse tumor models can be initiated in adult mice through Cre-recombinase-induced activation of oncogenic ...

    journal_title:Genes & development

    pub_type: 杂志文章,评审

    doi:10.1101/gad.1284505

    authors: Meuwissen R,Berns A

    更新日期:2005-03-15 00:00:00

  • Nanotechnology: emerging tools for biology and medicine.

    abstract::Historically, biomedical research has been based on two paradigms. First, measurements of biological behaviors have been based on bulk assays that average over large populations. Second, these behaviors have then been crudely perturbed by systemic administration of therapeutic treatments. Nanotechnology has the potent...

    journal_title:Genes & development

    pub_type: 杂志文章,评审

    doi:10.1101/gad.226837.113

    authors: Wong IY,Bhatia SN,Toner M

    更新日期:2013-11-15 00:00:00

  • A TIN2 dyskeratosis congenita mutation causes telomerase-independent telomere shortening in mice.

    abstract::The progressive bone marrow failure syndrome dyskeratosis congenita (DC) is often caused by mutations in telomerase or the factors involved in telomerase biogenesis and trafficking. However, a subset of DC patients is heterozygous for mutations in the shelterin component TIN2. To determine how the TIN2-DC mutations af...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.233395.113

    authors: Frescas D,de Lange T

    更新日期:2014-01-15 00:00:00

  • Transcriptional coactivators PGC-1alpha and PGC-lbeta control overlapping programs required for perinatal maturation of the heart.

    abstract::Oxidative tissues such as heart undergo a dramatic perinatal mitochondrial biogenesis to meet the high-energy demands after birth. PPARgamma coactivator-1 (PGC-1) alpha and beta have been implicated in the transcriptional control of cellular energy metabolism. Mice with combined deficiency of PGC-1alpha and PGC-1beta ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1661708

    authors: Lai L,Leone TC,Zechner C,Schaeffer PJ,Kelly SM,Flanagan DP,Medeiros DM,Kovacs A,Kelly DP

    更新日期:2008-07-15 00:00:00