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, the lethal phenotype precluded further analysis of the role of C/EBP alpha in hepatic gene regulation in adult mice. To circumvent this problem, we constructed a conditional knockout allele of c/ebp alpha by using the Cre/loxP recombination system. Homozygous c/ebp-loxP mice, (c/ebp alpha(fl/fl);fl, flanked by loxP sites) were found to be indistinguishable from their wild-type counterparts. However, when Cre recombinase was delivered to hepatocytes of adult c/ebp alpha(fl/fl) mice by infusion of a recombinant adenovirus carrying the cre gene, more than 80% of the c/ebp alpha(fl/fl) genes were deleted specifically in liver and C/EBP alpha expression was reduced by 90%. This condition resulted in a reduced level of bilirubin UDP-glucuronosyltransferase expression in the liver. After several days, the knockout mice developed severe jaundice due to an increase in unconjugated serum bilirubin. The expression of genes encoding phosphoenolpyruvate carboxykinase, glycogen synthase, and factor IX was also strongly reduced in adult conditional-knockout animals, while the expression of transferrin, apolipoprotein B, and insulin-like growth factor I genes was not affected. These results establish C/EBP alpha as an essential transcriptional regulator of genes encoding enzymes involved in bilirubin detoxification and gluconeogenesis in adult mouse liver.

journal_name

Mol Cell Biol

authors

Lee YH,Sauer B,Johnson PF,Gonzalez FJ

doi

10.1128/mcb.17.10.6014

subject

Has Abstract

pub_date

1997-10-01 00:00:00

pages

6014-22

issue

10

eissn

0270-7306

issn

1098-5549

journal_volume

17

pub_type

杂志文章
  • A transcriptional insulator element, the su(Hw) binding site, protects a chromosomal DNA replication origin from position effects.

    abstract::Eukaryotic chromosomes are organized into domains of activity for both transcription and DNA replication. Transcriptional "border," or "insulator," elements have been implicated in mediating the organization of transcriptional domains. However, the DNA sequence elements which might demarcate domains of DNA replication...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.4.2202

    authors: Lu L,Tower J

    更新日期:1997-04-01 00:00:00

  • Epigenetic regulation of transcription and virulence in Trypanosoma cruzi by O-linked thymine glucosylation of DNA.

    abstract::Unlike other eukaryotes, the protein-coding genes of Trypanosoma cruzi are arranged in large polycistronic gene clusters transcribed by polymerase II (Pol II). Thus, it is thought that trypanosomes rely solely on posttranscriptional processes to regulate gene expression. Here, we show that the glucosylated thymine DNA...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01277-10

    authors: Ekanayake DK,Minning T,Weatherly B,Gunasekera K,Nilsson D,Tarleton R,Ochsenreiter T,Sabatini R

    更新日期:2011-04-01 00:00:00

  • Addition of constitutive c-myc expression to Abelson murine leukemia virus changes the phenotype of the cells transformed by the virus from pre-B-cell lymphomas to plasmacytomas.

    abstract::Abelson murine leukemia virus (A-MuLV), a retrovirus that expresses the v-abl oncogene, characteristically induces pre-B-cell lymphomas following in vivo infection of BALB/c mice or in vitro infection of suspensions of fetal liver or bone marrow cells. ABL-MYC, a retrovirus that expresses both v-abl and c-myc, induces...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.4.2578

    authors: Weissinger EM,Mischak H,Goodnight J,Davidson WF,Mushinski JF

    更新日期:1993-04-01 00:00:00

  • The rhox homeobox gene cluster is imprinted and selectively targeted for regulation by histone h1 and DNA methylation.

    abstract::Histone H1 is an abundant and essential component of chromatin whose precise role in regulating gene expression is poorly understood. Here, we report that a major target of H1-mediated regulation in embryonic stem (ES) cells is the X-linked Rhox homeobox gene cluster. To address the underlying mechanism, we examined t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00734-10

    authors: Maclean JA,Bettegowda A,Kim BJ,Lou CH,Yang SM,Bhardwaj A,Shanker S,Hu Z,Fan Y,Eckardt S,McLaughlin KJ,Skoultchi AI,Wilkinson MF

    更新日期:2011-03-01 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

  • Binding of the termination factor Nsi1 to its cognate DNA site is sufficient to terminate RNA polymerase I transcription in vitro and to induce termination in vivo.

    abstract::Different models have been proposed explaining how eukaryotic gene transcription is terminated. Recently, Nsi1, a factor involved in silencing of ribosomal DNA (rDNA), was shown to be required for efficient termination of rDNA transcription by RNA polymerase I (Pol I) in the yeast Saccharomyces cerevisiae. Nsi1 contai...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00395-14

    authors: Merkl P,Perez-Fernandez J,Pilsl M,Reiter A,Williams L,Gerber J,Böhm M,Deutzmann R,Griesenbeck J,Milkereit P,Tschochner H

    更新日期:2014-10-01 00:00:00

  • Core binding factor cannot synergistically activate the myeloperoxidase proximal enhancer in immature myeloid cells without c-Myb.

    abstract::The myeloperoxidase (MPO) gene is transcribed specifically in immature myeloid cells and is regulated in part by a 414-bp proximal enhancer. Mutation of a core binding factor (CBF)-binding site at -288 decreased enhancer activity 30-fold in 32D cl3 myeloid cells cultured in granulocyte colony-stimulating factor (G-CSF...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.9.5127

    authors: Britos-Bray M,Friedman AD

    更新日期:1997-09-01 00:00:00

  • Null alleles of SAC7 suppress temperature-sensitive actin mutations in Saccharomyces cerevisiae.

    abstract::Extragenic suppressors of a new temperature-sensitive mutation (act1-4) in the actin gene of Saccharomyces cerevisiae were isolated in an attempt to identify genes whose products interact directly with actin. One suppressor with a cold-sensitive growth phenotype defined the new gene, SAC7, which was mapped, cloned, se...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.5.2308

    authors: Dunn TM,Shortle D

    更新日期:1990-05-01 00:00:00

  • Peroxisome proliferator-activated receptor alpha regulates a microRNA-mediated signaling cascade responsible for hepatocellular proliferation.

    abstract::Activation of peroxisome proliferator-activated receptor alpha (PPARalpha) leads to hepatocellular proliferation and liver carcinomas. The early events mediating these effects are unknown. A novel mechanism by which PPARalpha regulates gene expression and hepatocellular proliferation was uncovered. MicroRNA (miRNA) ex...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00317-07

    authors: Shah YM,Morimura K,Yang Q,Tanabe T,Takagi M,Gonzalez FJ

    更新日期:2007-06-01 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

  • The requirement of heat shock cognate 70 protein for mitochondrial import varies among precursor proteins and depends on precursor length.

    abstract::The cytosolic heat shock cognate 70-kDa protein (hsc70) is required for efficient import of ornithine transcarbamylase precursor (pOTC) into rat liver mitochondria (K. Terada, K. Ohtsuka, N. Imamoto, Y. Yoneda, and M. Mori, Mol. Cell. Biol. 15:3708-3713, 1995). The requirement of hsc70 for mitochondrial import of vari...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.11.6103

    authors: Terada K,Ueda I,Ohtsuka K,Oda T,Ichiyama A,Mori M

    更新日期:1996-11-01 00:00:00

  • Evolutionary conservation and predicted structure of the Drosophila extra sex combs repressor protein.

    abstract::The Drosophila extra sex combs (esc) protein, a member of the Polycomb group (PcG), is a transcriptional repressor of homeotic genes. Genetic studies have shown that esc protein is required in early embryos at about the time that other PcG proteins become engaged in homeotic gene repression. The esc protein consists p...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.11.6663

    authors: Ng J,Li R,Morgan K,Simon J

    更新日期:1997-11-01 00:00:00

  • Isolation and transcriptional characterization of three genes which function at start, the controlling event of the Saccharomyces cerevisiae cell division cycle: CDC36, CDC37, and CDC39.

    abstract::The genes CDC36, CDC37, and CDC39, thought to function in the cell division control process in Saccharomyces cerevisiae, were isolated from a recombinant plasmid library prepared by partial digestion of S. cerevisiae genomic DNA with Sau3A and insertion into the S. cerevisiae-Escherichia coli shuttle vector YRp7. In e...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.3.5.881

    authors: Breter HJ,Ferguson J,Peterson TA,Reed SI

    更新日期:1983-05-01 00:00:00

  • Activation of hematopoietic progenitor kinase 1 involves relocation, autophosphorylation, and transphosphorylation by protein kinase D1.

    abstract::Adaptive immune signaling can be coupled to stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) and NF-kappaB activation by the hematopoietic progenitor kinase 1 (HPK1), a mammalian hematopoiesis-specific Ste20 kinase. To gain insight into the regulation of leukocyte signal transduction, we investigat...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.6.2364-2383.2005

    authors: Arnold R,Patzak IM,Neuhaus B,Vancauwenbergh S,Veillette A,Van Lint J,Kiefer F

    更新日期:2005-03-01 00:00:00

  • Balance between distinct HP1 family proteins controls heterochromatin assembly in fission yeast.

    abstract::Heterochromatin protein 1 (HP1) is a conserved chromosomal protein with important roles in chromatin packaging and gene silencing. In fission yeast, two HP1 family proteins, Swi6 and Chp2, are involved in transcriptional silencing at heterochromatic regions, but how they function and whether they act cooperatively or ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00791-08

    authors: Sadaie M,Kawaguchi R,Ohtani Y,Arisaka F,Tanaka K,Shirahige K,Nakayama J

    更新日期:2008-12-01 00:00:00

  • Common factor 1 is a transcriptional activator which binds in the c-myc promoter, the skeletal alpha-actin promoter, and the immunoglobulin heavy-chain enhancer.

    abstract::Ubiquitously expressed transcription factors play an integral role in establishing and regulating patterns of gene transcription. Common factor 1 (CF1) is a ubiquitously expressed DNA-binding protein previously identified in our laboratory. We show here that CF1 recognizes sites in several diverse transcription elemen...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.3.1765

    authors: Riggs KJ,Merrell KT,Wilson G,Calame K

    更新日期:1991-03-01 00:00:00

  • Concerted functions of Gab1 and Shp2 in liver regeneration and hepatoprotection.

    abstract::Liver regeneration is a rapid and concerted response to injury, in which growth factor-generated intracellular signals result in activation of transcription factors, DNA synthesis, and hepatocyte proliferation. However, the link between cytoplasmic signals resulting in proliferative response to liver injury remains to...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.02253-05

    authors: Bard-Chapeau EA,Yuan J,Droin N,Long S,Zhang EE,Nguyen TV,Feng GS

    更新日期:2006-06-01 00:00:00

  • DNA-binding-defective mutants of the Epstein-Barr virus lytic switch activator Zta transactivate with altered specificities.

    abstract::The Epstein-Barr virus BRLF1 and BZLF1 genes are the first viral genes transcribed upon induction of the viral lytic cycle. The protein products of both genes (referred to here as Rta and Zta, respectively) activate expression of other viral genes, thereby initiating the lytic cascade. Among the viral antigens express...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.5.3041

    authors: Flemington EK,Lytle JP,Cayrol C,Borras AM,Speck SH

    更新日期:1994-05-01 00:00:00

  • Cancer-causing mutations in a novel transcription-dependent nuclear export motif of VHL abrogate oxygen-dependent degradation of hypoxia-inducible factor.

    abstract::It is thought that degradation of nuclear proteins by the ubiquitylation system requires nuclear-cytoplasmic trafficking of E3 ubiquitin ligases. The von Hippel-Lindau (VHL) tumor suppressor protein is the substrate recognition component of a Cullin-2-containing E3 ubiquitin ligase that recruits hypoxia-inducible fact...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01044-07

    authors: Khacho M,Mekhail K,Pilon-Larose K,Payette J,Lee S

    更新日期:2008-01-01 00:00:00

  • A network of mitogen-activated protein kinases links G protein-coupled receptors to the c-jun promoter: a role for c-Jun NH2-terminal kinase, p38s, and extracellular signal-regulated kinase 5.

    abstract::The expression of the c-jun proto-oncogene is rapidly induced in response to mitogens acting on a large variety of cell surface receptors. The resulting functional activity of c-Jun proteins appears to be critical for cell proliferation. Recently, we have shown that a large family of G protein-coupled receptors (GPCRs...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.6.4289

    authors: Marinissen MJ,Chiariello M,Pallante M,Gutkind JS

    更新日期:1999-06-01 00:00:00

  • Bcl2's flexible loop domain regulates p53 binding and survival.

    abstract::p53 not only functions as a transcription factor but also has a direct, apoptogenic role at the mitochondria. We have discovered that DNA damage-induced p53-Bcl2 binding is associated with decreased Bcl2-Bax interaction and increased apoptotic cell death in a mechanism regulated by Bcl2's flexible loop regulatory doma...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01647-05

    authors: Deng X,Gao F,Flagg T,Anderson J,May WS

    更新日期:2006-06-01 00:00:00

  • Novel DNA-binding proteins regulate intestine-specific transcription of the sucrase-isomaltase gene.

    abstract::Sucrase-isomaltase (SI) is an enterocyte-specific gene which exhibits a complex pattern of expression during intestinal development and in the adult intestinal mucosa. In the studies described in this report, we demonstrate that enterocyte-specific transcription of the SI gene is regulated by an evolutionarily conserv...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.8.3614

    authors: Traber PG,Wu GD,Wang W

    更新日期:1992-08-01 00:00:00

  • Abnormality in initiation program of DNA replication is monitored by the highly repetitive rRNA gene array on chromosome XII in budding yeast.

    abstract::We have shown previously that perturbation of origin firing in chromosome replication causes DNA lesions and triggers DNA damage checkpoint control, which ensures genomic integrity by stopping cell cycle progression until the lesions are repaired or by inducing cell death if they are not properly repaired. This was ba...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00731-06

    authors: Ide S,Watanabe K,Watanabe H,Shirahige K,Kobayashi T,Maki H

    更新日期:2007-01-01 00:00:00

  • RNA interference-mediated silencing of mitotic kinesin KIF14 disrupts cell cycle progression and induces cytokinesis failure.

    abstract::KIF14 is a microtubule motor protein whose elevated expression is associated with poor-prognosis breast cancer. Here we demonstrate KIF14 accumulation in mitotic cells, where it associated with developing spindle poles and spindle microtubules. Cells at later stages of mitosis were characterized by the concentration o...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.26.10.3853-3863.2006

    authors: Carleton M,Mao M,Biery M,Warrener P,Kim S,Buser C,Marshall CG,Fernandes C,Annis J,Linsley PS

    更新日期:2006-05-01 00:00:00

  • Comparison of the transactivation domains of Stat5 and Stat6 in lymphoid cells and mammary epithelial cells.

    abstract::Stat (signal transducers and activators of transcription) and Jak (Janus kinases) proteins are central components in the signal transduction events in hematopoietic and epithelial cells. They are rapidly activated by various cytokines, hormones, and growth factors. Upon ligand binding and cytokine receptor dimerizatio...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.7.3663

    authors: Moriggl R,Berchtold S,Friedrich K,Standke GJ,Kammer W,Heim M,Wissler M,Stöcklin E,Gouilleux F,Groner B

    更新日期:1997-07-01 00:00:00

  • Requirement of PDZ-containing proteins for cell cycle regulation and differentiation in the mouse lens epithelium.

    abstract::The roles of PDZ domain-containing proteins such as Dlg and Scrib have been well described for Drosophila; however, their requirement for mammalian development is poorly understood. Here we show that Dlg, Scrib, MAGI1, MAGI3, and MPDZ are expressed in the mouse ocular lens. We demonstrate that the increase in prolifer...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.24.8970-8981.2003

    authors: Nguyen MM,Nguyen ML,Caruana G,Bernstein A,Lambert PF,Griep AE

    更新日期:2003-12-01 00:00:00

  • Biochemical evidence for multiple independent emetine resistance genes in Chinese hamster cells.

    abstract::Hybridization-complementation studies indicated that mutations in multiple genes can render Chinese hamster cells resistant to the alkaloid translation inhibitor emetine. Two of the genes, emtA and emtB, recognized in Chinese hamster lung and ovary cell lines, respectively, are known to affect the ribosomes of the cel...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.3.2.198

    authors: Nielsen-Smith K,McGill S,Frahm M,Roufa DJ

    更新日期:1983-02-01 00:00:00

  • Domain-specific response of imprinted genes to reduced DNMT1.

    abstract::Imprinted genes are expressed in a monoallelic, parent-of-origin-specific manner. Clusters of imprinted genes are regulated by imprinting control regions (ICRs) characterized by DNA methylation of one allele. This methylation is critical for imprinting; a reduction in the DNA methyltransferase DNMT1 causes a widesprea...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01278-09

    authors: Weaver JR,Sarkisian G,Krapp C,Mager J,Mann MR,Bartolomei MS

    更新日期:2010-08-01 00:00:00

  • trkB, a neural receptor protein-tyrosine kinase: evidence for a full-length and two truncated receptors.

    abstract::We have screened an adult rat cerebellar cDNA library in search of novel protein tyrosine-kinase (PTK) cDNAs. A cDNA for a putative PTK, trkB, was cloned, and its sequence indicates that it is likely to be derived from a gene for a ligand-regulated receptor closely related to the human trk oncogene. Northern (RNA) ana...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.1.143

    authors: Middlemas DS,Lindberg RA,Hunter T

    更新日期:1991-01-01 00:00:00

  • 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