A ligand binding domain mutation in the mouse glucocorticoid receptor functionally links chromatin remodeling and transcription initiation.

Abstract:

:We utilized the mouse mammary tumor virus (MMTV) long terminal repeat (LTR) in vivo to understand how the interaction of the glucocorticoid receptor (GR) with a nucleosome-assembled promoter allows access of factors required for the transition from a repressed promoter to a derepressed, transcriptionally competent promoter. A mutation (C644G) in the ligand binding domain (LBD) of the mouse GR has provided information regarding the steps required in the derepression/activation process and in the functional significance of the two major transcriptional activation domains, AF1 and AF2. The mutant GR activates transcription from a transiently transfected promoter that has a disordered nucleosomal structure, though significantly less well than the wild-type GR. With an integrated, replicated promoter, which is assembled in an ordered nucleosomal array, the mutant GR does not activate transcription, and it fails to induce chromatin remodeling of the MMTV LTR promoter, as indicated by nuclease accessibility assays. Together, these findings support a two-step model for the transition of a nucleosome-assembled, repressed promoter to its transcriptionally active, derepressed form. In addition, we find that the C-terminal GR mutation is dominant over the transcription activation function of the N-terminal GR activation domain. These findings suggest that the primary activation function of the C-terminal activation domain is different from the function of the N-terminal activation domain and that it is required for derepression of the chromatin-repressed MMTV promoter.

journal_name

Mol Cell Biol

authors

Sheldon LA,Smith CL,Bodwell JE,Munck AU,Hager GL

doi

10.1128/mcb.19.12.8146

subject

Has Abstract

pub_date

1999-12-01 00:00:00

pages

8146-57

issue

12

eissn

0270-7306

issn

1098-5549

journal_volume

19

pub_type

杂志文章
  • A role for SMN exon 7 splicing in the selective vulnerability of motor neurons in spinal muscular atrophy.

    abstract::Spinal muscular atrophy (SMA) is an inherited motor neuron disease caused by homozygous loss of the Survival Motor Neuron 1 (SMN1) gene. In the absence of SMN1, inefficient inclusion of exon 7 in transcripts from the nearly identical SMN2 gene results in ubiquitous SMN decrease but selective motor neuron degeneration....

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.06077-11

    authors: Ruggiu M,McGovern VL,Lotti F,Saieva L,Li DK,Kariya S,Monani UR,Burghes AH,Pellizzoni L

    更新日期:2012-01-01 00:00:00

  • Nonsense-containing mRNAs that accumulate in the absence of a functional nonsense-mediated mRNA decay pathway are destabilized rapidly upon its restitution.

    abstract::Nonsense-mediated mRNA decay (NMD) is a conserved proofreading mechanism that protects eukaryotic cells from the potentially deleterious effects of truncated proteins. Studies of Saccharomyces cerevisiae imply that NMD is a predominantly cytoplasmic decay pathway, while studies of mammalian systems suggest that decay ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.3.842-851.2003

    authors: Maderazo AB,Belk JP,He F,Jacobson A

    更新日期:2003-02-01 00:00:00

  • Dominant negative mutants of transforming growth factor-beta 1 inhibit the secretion of different transforming growth factor-beta isoforms.

    abstract::Transforming growth factor-beta (TGF-beta) is a secreted polypeptide factor that is thought to play a major role in the regulation of proliferation of many cell types and various differentiation processes. Several related isoforms have been structurally characterized, three of which, TGF-beta 1, -beta 2, and -beta 3, ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.4.1674

    authors: Lopez AR,Cook J,Deininger PL,Derynck R

    更新日期:1992-04-01 00:00:00

  • AMF1 (GPS2) modulates p53 transactivation.

    abstract::We have reported that the papillomavirus E2 protein binds the nuclear factor AMF1 (also called G-protein pathway suppressor 2 or GPS2) and that their interaction is necessary for transcriptional activation by E2. It has also been shown that AMF1 can influence the activity of cellular transcription factors. These obser...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.21.17.5913-5924.2001

    authors: Peng YC,Kuo F,Breiding DE,Wang YF,Mansur CP,Androphy EJ

    更新日期:2001-09-01 00:00:00

  • The centrosomal, putative tumor suppressor protein TACC2 is dispensable for normal development, and deficiency does not lead to cancer.

    abstract::TACC2 is a member of the transforming acidic coiled-coil-containing protein family and is associated with the centrosome-spindle apparatus during cell cycling. In vivo, the TACC2 gene is expressed in various splice forms predominantly in postmitotic tissues, including heart, muscle, kidney, and brain. Studies of human...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.24.14.6403-6409.2004

    authors: Schuendeln MM,Piekorz RP,Wichmann C,Lee Y,McKinnon PJ,Boyd K,Takahashi Y,Ihle JN

    更新日期:2004-07-01 00:00:00

  • The capable ABL: what is its biological function?

    abstract::The mammalian ABL1 gene encodes the ubiquitously expressed nonreceptor tyrosine kinase ABL. In response to growth factors, cytokines, cell adhesion, DNA damage, oxidative stress, and other signals, ABL is activated to stimulate cell proliferation or differentiation, survival or death, retraction, or migration. ABL als...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章,评审

    doi:10.1128/MCB.01454-13

    authors: Wang JY

    更新日期:2014-04-01 00:00:00

  • Glucose-regulated protein (GRP94 and GRP78) genes share common regulatory domains and are coordinately regulated by common trans-acting factors.

    abstract::We isolated the promoter of the human gene encoding the 94,000-dalton glucose-regulated protein (GRP94). The 5'-flanking region important for its expression was identified by deletion analysis. Comparison of the promoters of the genes for GRP78 and GRP94 derived from human, rat, and chicken cells revealed a common dom...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.5.2153

    authors: Chang SC,Erwin AE,Lee AS

    更新日期:1989-05-01 00:00:00

  • Characterization of pp85, a target of oncogenes and growth factor receptors.

    abstract::An 85,000-molecular-weight polypeptide (85K polypeptide) has previously been identified as a common substrate for tyrosine phosphorylation upon polyomavirus middle T transformation or upon platelet-derived growth factor stimulation of 3T3 cells. In each case, pp85 has an associated phosphatidylinositol kinase activity...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.6.2909

    authors: Cohen B,Liu YX,Druker B,Roberts TM,Schaffhausen BS

    更新日期:1990-06-01 00:00:00

  • A vascular gene trap screen defines RasGRP3 as an angiogenesis-regulated gene required for the endothelial response to phorbol esters.

    abstract::We identified Ras guanine-releasing protein 3 (RasGRP3) as a guanine exchange factor expressed in blood vessels via an embryonic stem (ES) cell-based gene trap screen to identify novel vascular genes. RasGRP3 is expressed in embryonic blood vessels, down-regulated in mature adult vessels, and reexpressed in newly form...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.24.24.10515-10528.2004

    authors: Roberts DM,Anderson AL,Hidaka M,Swetenburg RL,Patterson C,Stanford WL,Bautch VL

    更新日期:2004-12-01 00:00:00

  • A proline-rich sequence unique to MEK1 and MEK2 is required for raf binding and regulates MEK function.

    abstract::Mammalian MEK1 and MEK2 contain a proline-rich (PR) sequence that is absent both from the yeast homologs Ste7 and Byr1 and from a recently cloned activator of the JNK/stress-activated protein kinases, SEK1/MKK4. Since this PR sequence occurs in MEKs that are regulated by Raf family enzymes but is missing from MEKs and...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.10.5214

    authors: Catling AD,Schaeffer HJ,Reuter CW,Reddy GR,Weber MJ

    更新日期:1995-10-01 00:00:00

  • Characterization of NF-kappa B/I kappa B proteins in zebra fish and their involvement in notochord development.

    abstract::Although largely involved in innate and adaptive immunity, NF-kappa B plays an important role in vertebrate development. In chicks, the inactivation of the NF-kappa B pathway induces functional alterations of the apical ectodermal ridge, which mediates limb outgrowth. In mice, the complete absence of NF-kappa B activi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.24.12.5257-5268.2004

    authors: Correa RG,Tergaonkar V,Ng JK,Dubova I,Izpisua-Belmonte JC,Verma IM

    更新日期:2004-06-01 00:00:00

  • Oligomerization of ETO is obligatory for corepressor interaction.

    abstract::Nearly 40% of cases of acute myelogenous leukemia (AML) of the M2 subtype are due to a chromosomal translocation that combines a sequence-specific DNA binding protein, AML1, with a potent transcriptional repressor, ETO. ETO interacts with nuclear receptor corepressors SMRT and N-CoR, which recruit histone deacetylase ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.1.156-163.2001

    authors: Zhang J,Hug BA,Huang EY,Chen CW,Gelmetti V,Maccarana M,Minucci S,Pelicci PG,Lazar MA

    更新日期:2001-01-01 00:00:00

  • Phosphorylation-dependent interaction of SATB1 and PIAS1 directs SUMO-regulated caspase cleavage of SATB1.

    abstract::Special AT-rich sequence-binding protein 1 (SATB1) is a tissue-restricted genome organizer that provides a key link between DNA loop organization, chromatin modification/remodeling, and transcription factor association at matrix attachment regions (MARs). The SUMO E3 ligase PIAS1 enhances SUMO conjugation to SATB1 lys...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01603-09

    authors: Tan JA,Song J,Chen Y,Durrin LK

    更新日期:2010-06-01 00:00:00

  • Differential activation of the Ras/extracellular-signal-regulated protein kinase pathway is responsible for the biological consequences induced by the Axl receptor tyrosine kinase.

    abstract::To understand the mechanism of Axl signaling, we have initiated studies to delineate downstream components in interleukin-3-dependent 32D cells by using a chimeric receptor containing the recombinant epidermal growth factor (EGF) receptor extracellular and transmembrane domains and the Axl kinase domain (EAK [for EGF ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.1.135

    authors: Fridell YW,Jin Y,Quilliam LA,Burchert A,McCloskey P,Spizz G,Varnum B,Der C,Liu ET

    更新日期:1996-01-01 00:00:00

  • Cloning of GT box-binding proteins: a novel Sp1 multigene family regulating T-cell receptor gene expression.

    abstract::Analysis of a T-cell antigen receptor (TCR) alpha promoter from a variable gene segment (V) revealed a critical GT box element which is also found in upstream regions of several V alpha genes, TCR enhancer, and regulatory elements of other genes. This element is necessary for TCR gene expression and binds several prot...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.10.4251

    authors: Kingsley C,Winoto A

    更新日期:1992-10-01 00:00:00

  • Analysis of the Role of the C-Terminal Tail in the Regulation of the Epidermal Growth Factor Receptor.

    abstract::The ∼230-residue C-terminal tail of the epidermal growth factor receptor (EGFR) is phosphorylated upon activation. We examined whether this phosphorylation is affected by deletions within the tail and whether the two tails in the asymmetric active EGFR dimer are phosphorylated differently. We monitored autophosphoryla...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00248-15

    authors: Kovacs E,Das R,Wang Q,Collier TS,Cantor A,Huang Y,Wong K,Mirza A,Barros T,Grob P,Jura N,Bose R,Kuriyan J

    更新日期:2015-09-01 00:00:00

  • Enhancer-dependent transcriptional oscillations in mouse erythroleukemia cells.

    abstract::By using recombinase-mediated cassette exchange, a method that allows integration of single copies of different constructs at the same predetermined chromosomal location, several expression cassettes have been integrated at a randomly chosen locus in the genome of mouse erythroleukemia cells. The cassettes studied con...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.7.4907

    authors: Feng YQ,Alami R,Bouhassira EE

    更新日期:1999-07-01 00:00:00

  • Polyamines regulate the stability of JunD mRNA by modulating the competitive binding of its 3' untranslated region to HuR and AUF1.

    abstract::Polyamines critically regulate all mammalian cell growth and proliferation by mechanisms such as the repression of growth-inhibitory proteins, including JunD. Decreasing the levels of cellular polyamines stabilizes JunD mRNA without affecting its transcription, but the exact mechanism whereby polyamines regulate JunD ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00807-10

    authors: Zou T,Rao JN,Liu L,Xiao L,Yu TX,Jiang P,Gorospe M,Wang JY

    更新日期:2010-11-01 00:00:00

  • Serum response factor and protein-mediated DNA bending contribute to transcription of the dystrophin muscle-specific promoter.

    abstract::The minimal muscle-specific dystrophin promoter contains the consensus sequence CC(A/T)6GG, or the CArG element, which can be found in serum-inducible or muscle-specific promoters. The serum response factor (SRF), which mediates the transcriptional activation of the c-fos gene in response to serum stimulation, can bin...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.3.1731

    authors: Galvagni F,Lestingi M,Cartocci E,Oliviero S

    更新日期:1997-03-01 00:00:00

  • High-frequency cotransformation by copolymerization of plasmids in the fission yeast Schizosaccharomyces pombe.

    abstract::We have developed a high-frequency cotransformation system which is useful in introducing nonreplicating circular DNA plasmids into the fission yeast Schizosaccharomyces pombe. This system depends on two factors: the ability of the ural-complementing helper plasmids pFYM2 and pFYM225 to propagate autonomously in S. po...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.4.4.651

    authors: Sakai K,Sakaguchi J,Yamamoto M

    更新日期:1984-04-01 00:00:00

  • ATP-dependent chromatin remodeling by the Cockayne syndrome B DNA repair-transcription-coupling factor.

    abstract::The Cockayne syndrome B protein (CSB) is required for coupling DNA excision repair to transcription in a process known as transcription-coupled repair (TCR). Cockayne syndrome patients show UV sensitivity and severe neurodevelopmental abnormalities. CSB is a DNA-dependent ATPase of the SWI2/SNF2 family. SWI2/SNF2-like...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.20.7643-7653.2000

    authors: Citterio E,Van Den Boom V,Schnitzler G,Kanaar R,Bonte E,Kingston RE,Hoeijmakers JH,Vermeulen W

    更新日期:2000-10-01 00:00:00

  • Dominant positive and negative selection using a hygromycin phosphotransferase-thymidine kinase fusion gene.

    abstract::The hygromycin phosphotransferase gene was fused in-frame with the herpes simplex virus type 1 thymidine kinase gene. The resulting fusion gene (termed HyTK) confers hygromycin B resistance for dominant positive selection and ganciclovir sensitivity for negative selection and provides a means by which these selectable...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.6.3374

    authors: Lupton SD,Brunton LL,Kalberg VA,Overell RW

    更新日期:1991-06-01 00:00:00

  • Inhibition of v-raf-dependent c-fos expression and transformation by a kinase-defective mutant of the mitogen-activated protein kinase Erk2.

    abstract::Receptor-bound growth factors elicit intracellular signals that lead to the phosphorylation and activation of numerous intracellular kinases and transcription factors with consequent changes in patterns of gene expression. Several oncogene products are able to mimic these signals, resulting in cell transformation and ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.7.4815

    authors: Kortenjann M,Thomae O,Shaw PE

    更新日期:1994-07-01 00:00:00

  • A conserved docking motif for CK1 binding controls the nuclear localization of NFAT1.

    abstract::In resting cells, the NFAT1 transcription factor is kept inactive in the cytoplasm by phosphorylation on multiple serine residues. These phosphorylated residues are primarily contained within two types of serine-rich motifs, the SRR-1 and SP motifs, which are conserved within the NFAT family. Several different kinases...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.24.10.4184-4195.2004

    authors: Okamura H,Garcia-Rodriguez C,Martinson H,Qin J,Virshup DM,Rao A

    更新日期:2004-05-01 00:00:00

  • RNA polymerase II accumulation in the promoter-proximal region of the dihydrofolate reductase and gamma-actin genes.

    abstract::The carboxyl-terminal domain (CTD) of RNA polymerase II (Pol II) can be phosphorylated at serine 2 (Ser-2) and serine 5 (Ser-5) of the CTD heptad repeat YSPTSPS, and this phosphorylation is important in coupling transcription to RNA processing, including 5' capping, splicing, and polyadenylation. The mammalian endogen...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.6.1961-1967.2003

    authors: Cheng C,Sharp PA

    更新日期:2003-03-01 00:00:00

  • A role for c-myc in chemically induced renal-cell death.

    abstract::A variety of genes, including c-myc, are activated by chemical toxicants in vivo and in vitro. Although enforced c-myc expression induces apoptosis after withdrawing survival factors, it is not clear if activation of the endogenous c-myc gene is an apoptotic signal after toxicant exposure. The renal tubular epithelium...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.11.6755

    authors: Zhan Y,Cleveland JL,Stevens JL

    更新日期:1997-11-01 00:00:00

  • Circadian and light-induced transcription of clock gene Per1 depends on histone acetylation and deacetylation.

    abstract::Circadian clock genes are regulated through a transcriptional-translational feedback loop. Alterations of the chromatin structure by histone acetyltransferases and histone deacetylases (HDACs) are commonly implicated in the regulation of gene transcription. However, little is known about the transcriptional regulation...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.24.14.6278-6287.2004

    authors: Naruse Y,Oh-hashi K,Iijima N,Naruse M,Yoshioka H,Tanaka M

    更新日期:2004-07-01 00:00:00

  • Gamma rays and bleomycin nick DNA and reverse the DNase I sensitivity of beta-globin gene chromatin in vivo.

    abstract::The active beta-globin genes in chicken erythrocytes, like all active genes, reside in large chromatin domains which are preferentially sensitive to digestion by DNase I. We have recently proposed that the special structure of chromatin in active domains is maintained by torsional stress in the DNA (Villeponteau et al...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.5.1917

    authors: Villeponteau B,Martinson HG

    更新日期:1987-05-01 00:00:00

  • Native polycystin 2 functions as a plasma membrane Ca2+-permeable cation channel in renal epithelia.

    abstract::Mutations in polycystin 2 (PC2), a Ca(2+)-permeable cation channel, cause autosomal dominant polycystic kidney disease. Whether PC2 functions in the endoplasmic reticulum (ER) or in the plasma membrane has been controversial. Here we generated and characterized a polyclonal antibody against PC2, determined the subcell...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.7.2600-2607.2003

    authors: Luo Y,Vassilev PM,Li X,Kawanabe Y,Zhou J

    更新日期:2003-04-01 00:00:00

  • Different cis-acting DNA elements control expression of the human apolipoprotein AI gene in different cell types.

    abstract::In mammals, the gene coding for apolipoprotein AI (apoAI), a protein of the plasma lipid transport system, is expressed only in the liver and the intestine. A series of plasmids containing various lengths of sequences flanking the 5' end of the human apoAI gene were constructed and assayed for transient expression aft...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.2.605

    authors: Sastry KN,Seedorf U,Karathanasis SK

    更新日期:1988-02-01 00:00:00