Neuropathy-associated Egr2 mutants disrupt cooperative activation of myelin protein zero by Egr2 and Sox10.

Abstract:

:Dominant mutations in the early growth response 2 (Egr2/Krox20) transactivator, a critical regulator of peripheral myelin development, have been associated with peripheral myelinopathies. These dominant mutants interfere with the expression of genes required for myelination by Schwann cells, including that for the most abundant peripheral myelin protein, Myelin protein zero (Mpz). In this study, we show that Egr2 mutants specifically affect an Egr2-responsive element within the Mpz first intron that also contains binding sites for the transcription factor Sox10. Furthermore, Egr2 activation through this element is impaired by mutation of the Sox10 binding sites. Using chromatin immunoprecipitation assays, we found that Egr2 and Sox10 bind to this element in myelinating sciatic nerve and that a dominant Egr2 mutant does not perturb Egr2 binding but rather attenuates binding of Sox10 to the Mpz intron element. Sox10 binding at other sites of Egr2/Sox10 synergy, including a novel site in the Myelin-associated glycoprotein (Mag) gene, is also reduced by the dominant Egr2 mutant. These results provide the first demonstration of binding of Egr2/Sox10 to adjacent sites in vivo and also demonstrate that neuropathy-associated Egr2 mutants antagonize binding of Sox10 at specific sites, thereby disrupting genetic control of the myelination program.

journal_name

Mol Cell Biol

authors

LeBlanc SE,Ward RM,Svaren J

doi

10.1128/MCB.01689-06

subject

Has Abstract

pub_date

2007-05-01 00:00:00

pages

3521-9

issue

9

eissn

0270-7306

issn

1098-5549

pii

MCB.01689-06

journal_volume

27

pub_type

杂志文章
  • Differential transactivation by the p53 transcription factor is highly dependent on p53 level and promoter target sequence.

    abstract::Little is known about the mechanisms that regulate differential transactivation by p53. We developed a system in the yeast Saccharomyces cerevisiae that addresses p53 transactivation capacity from 26 different p53 response elements (REs) under conditions where all other factors, such as chromatin, are kept constant. T...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.24.8612-8625.2002

    authors: Inga A,Storici F,Darden TA,Resnick MA

    更新日期:2002-12-01 00:00:00

  • Miz1 is required for early embryonic development during gastrulation.

    abstract::Miz1 is a member of the POZ domain/zinc finger transcription factor family. In vivo, Miz1 forms a complex with the Myc oncoprotein and recruits Myc to core promoter elements. Myc represses transcription through Miz1 binding sites. We now show that the Miz1 gene is ubiquitously expressed during mouse embryogenesis. In ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.21.7648-7657.2003

    authors: Adhikary S,Peukert K,Karsunky H,Beuger V,Lutz W,Elsässer HP,Möröy T,Eilers M

    更新日期:2003-11-01 00:00:00

  • Simian virus 40 major late promoter: an upstream DNA sequence required for efficient in vitro transcription.

    abstract::We have previously identified an 11-base DNA sequence, 5'-G-G-T-A-C-C-T-A-A-C-C-3' (simian virus 40 [SV40] map position 294 to 304), which is important in the control of SV40 late RNA expression in vitro and in vivo (Brady et al., Cell 31:625-633, 1982). We report here the identification of another domain of the SV40 ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.4.1.133

    authors: Brady J,Radonovich M,Thoren M,Das G,Salzman NP

    更新日期:1984-01-01 00:00:00

  • Amino-terminal extension generated from an upstream AUG codon increases the efficiency of mitochondrial import of yeast N2,N2-dimethylguanosine-specific tRNA methyltransferases.

    abstract::Fusions between the TRM1 gene of Saccharomyces cerevisiae and COXIV or DHFR were made to examine the mitochondrial targeting signals of N2,N2-dimethylguanosine-specific tRNA methyltransferase [tRNA (m2(2)G)dimethyltransferase]. This enzyme is responsible for the modification of both mitochondrial and cytoplasmic tRNAs...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.4.1611

    authors: Ellis SR,Hopper AK,Martin NC

    更新日期:1989-04-01 00:00:00

  • Disruption of the c/ebp alpha gene in adult mouse liver.

    abstract::The liver-enriched transcription factor C/EBP alpha has been implicated in the regulation of numerous liver-specific genes. It was previously reported that mice carrying a homozygous null mutation at the c/ebp alpha locus died as neonates due to the absence of hepatic glycogen and the resulting hypoglycemia. However, ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.10.6014

    authors: Lee YH,Sauer B,Johnson PF,Gonzalez FJ

    更新日期:1997-10-01 00:00:00

  • Central role for the XRCC1 BRCT I domain in mammalian DNA single-strand break repair.

    abstract::The DNA single-strand break repair (SSBR) protein XRCC1 is required for genetic stability and for embryonic viability. XRCC1 possesses two BRCA1 carboxyl-terminal (BRCT) protein interaction domains, denoted BRCT I and II. BRCT II is required for SSBR during G(1) but is dispensable for this process during S/G(2) and co...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.8.2556-2563.2002

    authors: Taylor RM,Thistlethwaite A,Caldecott KW

    更新日期:2002-04-01 00:00:00

  • Distinct subdomains of human TAFII130 are required for interactions with glutamine-rich transcriptional activators.

    abstract::TFIID is a multiprotein complex consisting of the TATA box binding protein and multiple tightly associated proteins (TAFIIs) that are required for transcription by selected activators. We previously reported cloning and partial characterization of human TAFII130 (hTAFII130). The central domain of hTAFII130 contains fo...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.10.5734

    authors: Saluja D,Vassallo MF,Tanese N

    更新日期:1998-10-01 00:00:00

  • Termination region in rRNA genes from a eucaryotic thermophile, Thermomyces lanuginosus.

    abstract::S1 mapping of the termination region in the ribosomal DNA from a thermophilic fungus, Thermomyces lanuginosus, revealed three distinct termini corresponding to the mature 25S rRNA, a precursor that is 19 nucleotides longer and corresponds to the 37S precursor in yeast cells, and a putative termination site at +96 that...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.1.377

    authors: Walker K,Wong WM,Nazar RN

    更新日期:1990-01-01 00:00:00

  • A conserved alpha-helical motif mediates the interaction of Sp1-like transcriptional repressors with the corepressor mSin3A.

    abstract::Sp1-like proteins are defined by three highly homologous C(2)H(2) zinc finger motifs that bind GC-rich sequences found in the promoters of a large number of genes essential for mammalian cell homeostasis. Here we report that TIEG2, a transforming growth factor beta-inducible Sp1-like protein with antiproliferative fun...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.15.5041-5049.2001

    authors: Zhang JS,Moncrieffe MC,Kaczynski J,Ellenrieder V,Prendergast FG,Urrutia R

    更新日期:2001-08-01 00:00:00

  • Different genetic functions for the Rpd3(L) and Rpd3(S) complexes suggest competition between NuA4 and Rpd3(S).

    abstract::Rpd3(L) and Rpd3(S) are distinct multisubunit complexes containing the Rpd3 histone deacetylase. Disruption of the GCN5 histone acetyltransferase gene shows a strong synthetic phenotype when combined with either an sds3 mutation affecting only the Rpd3(L) complex or an rco1 mutation affecting only Rpd3(S). However, th...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00164-08

    authors: Biswas D,Takahata S,Stillman DJ

    更新日期:2008-07-01 00:00:00

  • Gamma interferon modulates myogenesis through the major histocompatibility complex class II transactivator, CIITA.

    abstract::Gamma interferon (IFN-γ) is an inflammatory cytokine that has complex effects on myogenesis. Here, we show that the IFN-γ-induced inhibition of myogenesis is mediated by the major histocompatibility complex (MHC) class II transactivator, CIITA, which binds to myogenin and inhibits its activity. In IFN-γ-treated myobla...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.05397-11

    authors: Londhe P,Davie JK

    更新日期:2011-07-01 00:00:00

  • In vivo mitochondrial p53 translocation triggers a rapid first wave of cell death in response to DNA damage that can precede p53 target gene activation.

    abstract::p53 promotes apoptosis in response to death stimuli by transactivation of target genes and by transcription-independent mechanisms. We recently showed that wild-type p53 rapidly translocates to mitochondria in response to multiple death stimuli in cultured cells. Mitochondrial p53 physically interacts with antiapoptot...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.24.15.6728-6741.2004

    authors: Erster S,Mihara M,Kim RH,Petrenko O,Moll UM

    更新日期:2004-08-01 00:00:00

  • Bcl-3 expression promotes cell survival following interleukin-4 deprivation and is controlled by AP1 and AP1-like transcription factors.

    abstract::We have analyzed the interleukin-4 (IL-4)-triggered mechanisms implicated in cell survival and show here that IL-4 deprivation induces apoptotic cell death but does not modulate Bcl-2 or Bcl-x expression. Since Bcl-x expression is insufficient to ensure cell survival in the absence of IL-4, we speculate that additiona...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.10.3407-3416.2000

    authors: Rebollo A,Dumoutier L,Renauld JC,Zaballos A,Ayllón V,Martínez-A C

    更新日期:2000-05-01 00:00:00

  • The three mouse multidrug resistance (mdr) genes are expressed in a tissue-specific manner in normal mouse tissues.

    abstract::The gene responsible for multidrug resistance (mdr), which encodes the P-glycoprotein, is a member of a multigene family. We have identified distinct mdr gene transcripts encoded by three separate mdr genes in the mouse. Expression levels of each mdr gene are dramatically different in various mouse tissues. Specific m...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.3.1346

    authors: Croop JM,Raymond M,Haber D,Devault A,Arceci RJ,Gros P,Housman DE

    更新日期:1989-03-01 00:00:00

  • Protein-damaging stresses activate c-Jun N-terminal kinase via inhibition of its dephosphorylation: a novel pathway controlled by HSP72.

    abstract::Various stresses activate the c-Jun N-terminal kinase (JNK), which is involved in the regulation of many aspects of cellular physiology, including apoptosis. Here we demonstrate that in contrast to UV irradiation, heat shock causes little or no stimulation of the JNK-activating kinase SEK1, while knocking out the SEK1...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.4.2547

    authors: Meriin AB,Yaglom JA,Gabai VL,Zon L,Ganiatsas S,Mosser DD,Zon L,Sherman MY

    更新日期:1999-04-01 00:00:00

  • Isolation of the Drosophila melanogaster dunce chromosomal region and recombinational mapping of dunce sequences with restriction site polymorphisms as genetic markers.

    abstract::Using the method of chromosomal walking, we have isolated a contiguous region of the Drosophila melanogaster X chromosome which corresponds to salivary gland chromosome bands 3C12 to 3D4. This five-band region contains approximately 100 kilobases of DNA, including those sequences comprising dunce, a gene which functio...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.4.2.358

    authors: Davis RL,Davidson N

    更新日期:1984-02-01 00:00:00

  • C-Terminal binding protein is a transcriptional repressor that interacts with a specific class of vertebrate Polycomb proteins.

    abstract::Polycomb (Pc) is part of a Pc group (PcG) protein complex that is involved in repression of gene activity during Drosophila and vertebrate development. To identify proteins that interact with vertebrate Pc homologs, we performed two-hybrid screens with Xenopus Pc (XPc) and human Pc 2 (HPC2). We find that the C-termina...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.1.777

    authors: Sewalt RG,Gunster MJ,van der Vlag J,Satijn DP,Otte AP

    更新日期:1999-01-01 00:00:00

  • Atypical protein kinase C phosphorylates Par6 and facilitates transforming growth factor β-induced epithelial-to-mesenchymal transition.

    abstract::Epithelial-to-mesenchymal transition (EMT) is controlled by cellular signaling pathways that trigger the loss of cell-cell adhesion and lead to the restructuring of the cell cytoskeleton. Transforming growth factor β (TGF-β) has been shown to regulate cell plasticity through the phosphorylation of Par6 on a conserved ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00837-12

    authors: Gunaratne A,Thai BL,Di Guglielmo GM

    更新日期:2013-03-01 00:00:00

  • Human and mouse MOK2 proteins are associated with nuclear ribonucleoprotein components and bind specifically to RNA and DNA through their zinc finger domains.

    abstract::The human and murine MOK2 ortholog genes that are preferentially expressed in brain and testis tissues encode two different Krüppel-like zinc finger proteins. In this paper, we show that the MOK2 proteins are mainly associated with nuclear ribonucleoprotein components, including the nucleoli and extranucleolar structu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.4.2116

    authors: Arranz V,Harper F,Florentin Y,Puvion E,Kress M,Ernoult-Lange M

    更新日期:1997-04-01 00:00:00

  • Stimulation of transcription factor binding and histone displacement by nucleosome assembly protein 1 and nucleoplasmin requires disruption of the histone octamer.

    abstract::To investigate the mechanisms by which transcription factors invade nucleosomal DNA and replace histones at control elements, we have examined the response of the histone octamer to transcription factor binding in the presence of histone-binding proteins (i.e., nucleosome assembly factors). We found that yeast nucleos...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.11.6178

    authors: Walter PP,Owen-Hughes TA,Côté J,Workman JL

    更新日期:1995-11-01 00:00:00

  • Functional interaction between p53, the TATA-binding protein (TBP), andTBP-associated factors in vivo.

    abstract::The transcriptional activator p53 is known to interact with components of the general transcription factor TFIID in vitro. To examine the relevance of these associations to transcriptional activation in vivo, plasmids expressing a p53-GAL4 chimera and Drosophila TATA-binding protein (dTBP) were transfected into Drosop...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.8.4295

    authors: Farmer G,Colgan J,Nakatani Y,Manley JL,Prives C

    更新日期:1996-08-01 00:00:00

  • Induction of meiosis in Saccharomyces cerevisiae depends on conversion of the transcriptional represssor Ume6 to a positive regulator by its regulated association with the transcriptional activator Ime1.

    abstract::The transcription of meiosis-specific genes, as well as the initiation of meiosis, in the budding yeast Saccharomyces cerevisiae depends on IME1. IME1 encodes a transcriptional activator which lacks known DNA binding motifs. In this study we have determined the mode by which Ime1 specifically activates the transcripti...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.5.2518

    authors: Rubin-Bejerano I,Mandel S,Robzyk K,Kassir Y

    更新日期:1996-05-01 00:00:00

  • Intestinal master transcription factor CDX2 controls chromatin access for partner transcription factor binding.

    abstract::Tissue-specific gene expression requires modulation of nucleosomes, allowing transcription factors to occupy cis elements that are accessible only in selected tissues. Master transcription factors control cell-specific genes and define cellular identities, but it is unclear if they possess special abilities to regulat...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01185-12

    authors: Verzi MP,Shin H,San Roman AK,Liu XS,Shivdasani RA

    更新日期:2013-01-01 00:00:00

  • Proteomics of the eukaryotic transcription machinery: identification of proteins associated with components of yeast TFIID by multidimensional mass spectrometry.

    abstract::The general transcription factor TFIID is a multisubunit complex of TATA-binding protein (TBP) and 14 distinct TBP-associated factors (TAFs). Although TFIID constituents are required for transcription initiation of most mRNA encoding genes, the mechanism of TFIID action remains unclear. To gain insight into TFIID func...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.13.4723-4738.2002

    authors: Sanders SL,Jennings J,Canutescu A,Link AJ,Weil PA

    更新日期:2002-07-01 00:00:00

  • Identification of a new Pyk2 target protein with Arf-GAP activity.

    abstract::Protein tyrosine kinase Pyk2 is activated by a variety of G-protein-coupled receptors and by extracellular signals that elevate intracellular Ca2+ concentration. We have identified a new Pyk2 binding protein designated Pap. Pap is a multidomain protein composed of an N-terminal alpha-helical region with a coiled-coil ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.3.2338

    authors: Andreev J,Simon JP,Sabatini DD,Kam J,Plowman G,Randazzo PA,Schlessinger J

    更新日期:1999-03-01 00:00:00

  • The HOX homeodomain proteins block CBP histone acetyltransferase activity.

    abstract::Despite the identification of PBC proteins as cofactors that provide DNA affinity and binding specificity for the HOX homeodomain proteins, HOX proteins do not demonstrate robust activity in transient-transcription assays and few authentic downstream targets have been identified for these putative transcription factor...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.21.7509-7522.2001

    authors: Shen WF,Krishnan K,Lawrence HJ,Largman C

    更新日期:2001-11-01 00:00:00

  • NAB2, a corepressor of NGFI-A (Egr-1) and Krox20, is induced by proliferative and differentiative stimuli.

    abstract::Previous work had identified a corepressor, NAB1, which represses transcriptional activation mediated by NGFI-A (also known as Egr-1, zif268, and Krox24) and Krox20. These zinc finger transcription factors are encoded by immediate-early genes and have been implicated in a wide variety of proliferative and differentiat...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.7.3545

    authors: Svaren J,Sevetson BR,Apel ED,Zimonjic DB,Popescu NC,Milbrandt J

    更新日期:1996-07-01 00:00:00

  • Mitochondrial protein import: recognition of internal import signals of BCS1 by the TOM complex.

    abstract::BCS1, a component of the inner membrane of mitochondria, belongs to the group of proteins with internal, noncleavable import signals. Import and intramitochondrial sorting of BCS1 are encoded in the N-terminal 126 amino acid residues. Three sequence elements were identified in this region, namely, the transmembrane do...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.7.2239-2250.2003

    authors: Stan T,Brix J,Schneider-Mergener J,Pfanner N,Neupert W,Rapaport D

    更新日期:2003-04-01 00:00:00

  • Kinetics and regulation of the tyrosine phosphorylation of epidermal growth factor receptor in intact A431 cells.

    abstract::We have previously reported that antibodies to phosphotyrosine recognize the phosphorylated forms of platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) receptors (Zippel et al., Biochim. Biophys. Acta 881:54-61, 1986, and Sturani et al., Biochem. Biophys. Res. Commun. 137:343-350, 1986). In this r...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.3.1345

    authors: Sturani E,Zippel R,Toschi L,Morello L,Comoglio PM,Alberghina L

    更新日期:1988-03-01 00:00:00

  • N-ras mutations in human cutaneous melanoma from sun-exposed body sites.

    abstract::In 7 of 37 patients with cutaneous melanoma, mutations in the N-ras gene were found. The primary tumors of these seven patients were exclusively localized on body sites continuously exposed to sunlight. Moreover, the ras mutations were all at or near dipyrimidine sites known to be targets of UV damage. Two primary tum...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.7.3114

    authors: van 't Veer LJ,Burgering BM,Versteeg R,Boot AJ,Ruiter DJ,Osanto S,Schrier PI,Bos JL

    更新日期:1989-07-01 00:00:00