The CACCC-binding protein KLF3/BKLF represses a subset of KLF1/EKLF target genes and is required for proper erythroid maturation in vivo.

Abstract:

:The CACCC-box binding protein erythroid Krüppel-like factor (EKLF/KLF1) is a master regulator that directs the expression of many important erythroid genes. We have previously shown that EKLF drives transcription of the gene for a second KLF, basic Krüppel-like factor, or KLF3. We have now tested the in vivo role of KLF3 in erythroid cells by examining Klf3 knockout mice. KLF3-deficient adults exhibit a mild compensated anemia, including enlarged spleens, increased red pulp, and a higher percentage of erythroid progenitors, together with elevated reticulocytes and abnormal erythrocytes in the peripheral blood. Impaired erythroid maturation is also observed in the fetal liver. We have found that KLF3 levels rise as erythroid cells mature to become TER119(+). Consistent with this, microarray analysis of both TER119(-) and TER119(+) erythroid populations revealed that KLF3 is most critical at the later stages of erythroid maturation and is indeed primarily a transcriptional repressor. Notably, many of the genes repressed by KLF3 are also known to be activated by EKLF. However, the majority of these are not currently recognized as erythroid-cell-specific genes. These results reveal the molecular and physiological function of KLF3, defining it as a feedback repressor that counters the activity of EKLF at selected target genes to achieve normal erythropoiesis.

journal_name

Mol Cell Biol

authors

Funnell AP,Norton LJ,Mak KS,Burdach J,Artuz CM,Twine NA,Wilkins MR,Power CA,Hung TT,Perdomo J,Koh P,Bell-Anderson KS,Orkin SH,Fraser ST,Perkins AC,Pearson RC,Crossley M

doi

10.1128/MCB.00173-12

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

3281-92

issue

16

eissn

0270-7306

issn

1098-5549

pii

MCB.00173-12

journal_volume

32

pub_type

杂志文章
  • mRNA-decapping enzyme from Saccharomyces cerevisiae: purification and unique specificity for long RNA chains.

    abstract::An enzyme that hydrolyzes one PPi bond of the cap structure of mRNA, yielding m7GDP and 5'-p RNA was purified from Saccharomyces cerevisiae to a stage suitable for characterization. The specificity of the enzyme was studied, using both yeast mRNA and synthetic RNAs labeled in the cap structure. A synthetic capped RNA ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.5.2005

    authors: Stevens A

    更新日期:1988-05-01 00:00:00

  • Roles of vertebrate Smc5 in sister chromatid cohesion and homologous recombinational repair.

    abstract::The structural maintenance of chromosomes (Smc) family members Smc5 and Smc6 are both essential in budding and fission yeasts. Yeast smc5/6 mutants are hypersensitive to DNA damage, and Smc5/6 is recruited to HO-induced double-strand breaks (DSBs), facilitating intersister chromatid recombinational repair. To determin...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00786-10

    authors: Stephan AK,Kliszczak M,Dodson H,Cooley C,Morrison CG

    更新日期:2011-04-01 00:00:00

  • A human globin enhancer causes both discrete and widespread alterations in chromatin structure.

    abstract::Gene activation requires alteration of chromatin structure to facilitate active transcription complex formation at a gene promoter. Nucleosome remodeling complexes and histone modifying complexes each play unique and interdependent roles in bringing about these changes. The role of distant enhancers in these structura...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.22.8099-8109.2003

    authors: Kim A,Dean A

    更新日期:2003-11-01 00:00:00

  • Elements involved in S-adenosylmethionine-mediated regulation of the Saccharomyces cerevisiae MET25 gene.

    abstract::In Saccharomyces cerevisiae, the MET25 gene encodes O-acetylhomoserine sulfhydrylase. Synthesis of this enzyme is repressed by the presence of S-adenosylmethionine (AdoMet) in the growth medium. We identified cis elements required for MET25 expression by analyzing small deletions in the MET25 promoter region. The resu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.8.3292

    authors: Thomas D,Cherest H,Surdin-Kerjan Y

    更新日期:1989-08-01 00:00:00

  • The simian virus 40 sequences between 0.169 and 0.423 map units are not essential to immortalize early-passage rat embryo cells.

    abstract::F8dl is a simian virus 40 early-region deletion mutant that lacks the sequences between 0.169 and 0.423 map units. We show that cloned F8dl DNA immortalized early-passage Fisher rat embryo cells with an efficiency that was about 20% of that of cloned wild-type simian virus 40 DNA. In contrast, we detected no immortali...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.5.5.1191

    authors: Sompayrac L,Danna KJ

    更新日期:1985-05-01 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

  • C/EBPalpha is a DNA damage-inducible p53-regulated mediator of the G1 checkpoint in keratinocytes.

    abstract::The basic leucine zipper transcription factor, CCAAT/enhancer binding protein alpha (C/EBPalpha), is abundantly expressed in keratinocytes of the skin; however, its function in skin is poorly characterized. UVB radiation is responsible for the majority of human skin cancers. In response to UVB-induced DNA damage, kera...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.24.24.10650-10660.2004

    authors: Yoon K,Smart RC

    更新日期:2004-12-01 00:00:00

  • Major Egr3 isoforms are generated via alternate translation start sites and differ in their abilities to activate transcription.

    abstract::In previous studies, we detected a major, unidentified Egr response element (ERE) binding complex in brain extracts. We now report that this complex contains a truncated isoform of Egr3 generated by use of an alternate translation start site at methionine 106. Furthermore, the ERE binding complex previously thought to...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.7.4711

    authors: O'Donovan KJ,Baraban JM

    更新日期:1999-07-01 00:00:00

  • Regulation of urokinase-type plasminogen activator gene transcription by macrophage colony-stimulating factor.

    abstract::The mouse urokinase-type plasminogen activator (uPA) gene was used as a model macrophage colony-stimulating factor 1 (CSF-1)-inducible gene to investigate CSF-1 signalling pathways. Nuclear run-on analysis showed that induction of uPA mRNA by CSF-1 and phorbol myristate acetate (PMA) was at the transcriptional level i...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.6.3430

    authors: Stacey KJ,Fowles LF,Colman MS,Ostrowski MC,Hume DA

    更新日期:1995-06-01 00:00:00

  • Capn5 is expressed in a subset of T cells and is dispensable for development.

    abstract::The Capn5 gene was inactivated by homologous recombination in ES cells that subsequently colonized the germ line of mice. The targeted mutation integrated a lacZ expression cassette into the Capn5 gene, allowing the expression of Capn5 mRNA to be examined in detail in heterozygous animals. Expression was observed in e...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.24.4.1649-1654.2004

    authors: Franz T,Winckler L,Boehm T,Dear TN

    更新日期:2004-02-01 00:00:00

  • Regulation of calcineurin through transcriptional induction of the calcineurin A beta promoter in vitro and in vivo.

    abstract::The calcineurin-nuclear factor of activated T cells (NFAT) signaling pathway has been shown to be of critical importance in regulating the growth response of cardiac myocytes. We have previously demonstrated that calcineurin A(beta) (CnA(beta)) mRNA and protein are increased in response to growth stimulation, although...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.15.6649-6659.2005

    authors: Oka T,Dai YS,Molkentin JD

    更新日期:2005-08-01 00:00:00

  • Clusters of S1 nuclease-hypersensitive sites induced in vivo by DNA damage.

    abstract::DNA end-labeling procedures were used to analyze both the frequency and distribution of DNA strand breaks in mammalian cells exposed or not to different types of DNA-damaging agents. The 3' ends were labeled by T4 DNA polymerase-catalyzed nucleotide exchange carried out in the absence or presence of Escherichia coli e...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.9.5437

    authors: Legault J,Tremblay A,Ramotar D,Mirault ME

    更新日期:1997-09-01 00:00:00

  • TAPA-1, the target of an antiproliferative antibody, defines a new family of transmembrane proteins.

    abstract::A murine monoclonal antibody was identified by its ability to induce a reversible antiproliferative effect on a human lymphoma cell line. Immunoprecipitation studies revealed that the antibody reacted with a 26-kilodalton cell surface protein (TAPA-1). A diverse group of human cell lines, including hematolymphoid, neu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.8.4007

    authors: Oren R,Takahashi S,Doss C,Levy R,Levy S

    更新日期:1990-08-01 00:00:00

  • Cross Talk between Wnt/β-Catenin and CIP2A/Plk1 Signaling in Prostate Cancer: Promising Therapeutic Implications.

    abstract::Aberrant activation of the Wnt/β-catenin pathway and polo-like kinase 1 (Plk1) overexpression represent two common events in prostate cancer with relevant functional implications. This minireview analyzes their potential therapeutic significance in prostate cancer based on their role as androgen receptor (AR) signalin...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章,评审

    doi:10.1128/MCB.00130-16

    authors: Cristóbal I,Rojo F,Madoz-Gúrpide J,García-Foncillas J

    更新日期:2016-05-31 00:00:00

  • Characterization of factors that direct transcription of rat ribosomal DNA.

    abstract::The protein components that direct and activate accurate transcription by rat RNA polymerase I were studied in extracts of Novikoff hepatoma ascites cells. A minimum of at least two components, besides RNA polymerase I, that are necessary for efficient utilization of templates were identified. The first factor, rat SL...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.6.3105

    authors: Smith SD,Oriahi E,Lowe D,Yang-Yen HF,O'Mahony D,Rose K,Chen K,Rothblum LI

    更新日期:1990-06-01 00:00:00

  • Type 1 transforming growth factor beta: amplified expression and secretion of mature and precursor polypeptides in Chinese hamster ovary cells.

    abstract::Recombinant type 1 transforming growth factor beta (TGF-beta) was expressed to high levels in CHO cells by using dihydrofolate reductase (dhfr) gene amplification. The expression plasmid was derived from the pSV2 vectors and contained, in tandem, the simian TGF-beta and mouse dhfr cDNAs. Transcription of both cDNAs wa...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.10.3418

    authors: Gentry LE,Webb NR,Lim GJ,Brunner AM,Ranchalis JE,Twardzik DR,Lioubin MN,Marquardt H,Purchio AF

    更新日期:1987-10-01 00:00:00

  • A novel myoblast enhancer element mediates MyoD transcription.

    abstract::The MyoD gene can orchestrate the expression of the skeletal muscle differentiation program. We have identified the regions of the gene necessary to reproduce transcription specific to skeletal myoblasts and myotubes. A proximal regulatory region (PRR) contains a conserved TATA box, a CCAAT box, and a GC-rich region t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.11.4994

    authors: Tapscott SJ,Lassar AB,Weintraub H

    更新日期:1992-11-01 00:00:00

  • Androgen receptor acetylation governs trans activation and MEKK1-induced apoptosis without affecting in vitro sumoylation and trans-repression function.

    abstract::The androgen receptor (AR) is a nuclear hormone receptor superfamily member that conveys both trans repression and ligand-dependent trans-activation function. Activation of the AR by dihydrotestosterone (DHT) regulates diverse physiological functions including secondary sexual differentiation in the male and the induc...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.10.3373-3388.2002

    authors: Fu M,Wang C,Wang J,Zhang X,Sakamaki T,Yeung YG,Chang C,Hopp T,Fuqua SA,Jaffray E,Hay RT,Palvimo JJ,Jänne OA,Pestell RG

    更新日期:2002-05-01 00:00:00

  • Multiple proteins interact with the fushi tarazu proximal enhancer.

    abstract::The expression of the Drosophila segmentation gene fushi tarazu (ftz) is controlled at the level of transcription. The proximal enhancer, located approximately 3.4 kb upstream of the transcription start site, directs lacZ fusion gene expression in a ftz-like seven-stripe pattern in transgenic fly embryos. We have take...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.9.5549

    authors: Han W,Yu Y,Altan N,Pick L

    更新日期:1993-09-01 00:00:00

  • In vivo assembly of yeast mitochondrial alpha-ketoglutarate dehydrogenase complex.

    abstract::The assembly of alpha-ketoglutarate dehydrogenase complex (KGDC) has been studied in wild-type Saccharomyces cerevisiae and in respiratory-deficient strains (pet) with mutations in KGD1 and KGD2, the structural genes for alpha-ketoglutarate dehydrogenase (KE1) and dihydrolipoyl transsuccinylase (KE2) components, respe...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.8.3931

    authors: Repetto B,Tzagoloff A

    更新日期:1991-08-01 00:00:00

  • Insulin receptor substrates Irs1 and Irs2 coordinate skeletal muscle growth and metabolism via the Akt and AMPK pathways.

    abstract::Coordination of skeletal muscle growth and metabolism with nutrient availability is critical for metabolic homeostasis. To establish the role of insulin-like signaling in this process, we used muscle creatine kinase (MCK)-Cre to disrupt expression of insulin receptor substrates Irs1 and Irs2 in mouse skeletal/cardiac ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00983-10

    authors: Long YC,Cheng Z,Copps KD,White MF

    更新日期:2011-02-01 00:00:00

  • Negative regulatory gene for general control of amino acid biosynthesis in Saccharomyces cerevisiae.

    abstract::In Saccharomyces cerevisiae, many amino acid biosynthetic pathways are coregulated by a complex general control system: starvation for a single amino acid results in the derepression of amino acid biosynthetic genes in multiple pathways. Derepression of these genes is mediated by positive (GCN) and negative (GCD) regu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.6.9.3150

    authors: Myers PL,Skvirsky RC,Greenberg ML,Greer H

    更新日期:1986-09-01 00:00:00

  • The dual effect of Rac2 on phospholipase D2 regulation that explains both the onset and termination of chemotaxis.

    abstract::We document a biphasic effect of Rac2 on the activation and inhibition of PLD2. Cells overexpressing Rac2 and PLD2 simultaneously show a robust initial (<10 min) response toward a chemoattractant that is later (>30 min) greatly diminished over PLD2-only controls. The first phase is due to the presence of a Rac2-PLD2 p...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01348-10

    authors: Peng HJ,Henkels KM,Mahankali M,Marchal C,Bubulya P,Dinauer MC,Gomez-Cambronero J

    更新日期:2011-06-01 00:00:00

  • Ras is required for the cyclic AMP-dependent activation of Rap1 via Epac2.

    abstract::Exchange proteins activated by cAMP (cyclic AMP) 2 (Epac2) is a guanine nucleotide exchange factor for Rap1, a small G protein involved in many cellular functions, including cell adhesion, differentiation, and exocytosis. Epac2 interacts with Ras-GTP via a Ras association (RA) domain. Previous studies have suggested t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01060-08

    authors: Liu C,Takahashi M,Li Y,Song S,Dillon TJ,Shinde U,Stork PJ

    更新日期:2008-12-01 00:00:00

  • In vitro posttranslational modification of lamin B cloned from a human T-cell line.

    abstract::Autoimmune diseases are characterized by spontaneously occurring autoantibodies which have proven to be useful reagents for the characterization of specific nuclear proteins. Using a monoclonal autoantibody (72B9) derived from a murine lupus strain, we have cloned a cDNA from the human T-cell line MOLT-4, which encode...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.5.2164

    authors: Pollard KM,Chan EK,Grant BJ,Sullivan KF,Tan EM,Glass CA

    更新日期:1990-05-01 00:00:00

  • Alkylpurine-DNA-N-glycosylase knockout mice show increased susceptibility to induction of mutations by methyl methanesulfonate.

    abstract::Alkylpurine-DNA-N-glycosylase (APNG) null mice have been generated by homologous recombination in embryonic stem cells. The null status of the animals was confirmed at the mRNA level by reverse transcription-PCR and by the inability of cell extracts of tissues from the knockout (ko) animals to release 3-methyladenine ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.10.5828

    authors: Elder RH,Jansen JG,Weeks RJ,Willington MA,Deans B,Watson AJ,Mynett KJ,Bailey JA,Cooper DP,Rafferty JA,Heeran MC,Wijnhoven SW,van Zeeland AA,Margison GP

    更新日期:1998-10-01 00:00:00

  • A new function for a phosphotyrosine phosphatase: linking GRB2-Sos to a receptor tyrosine kinase.

    abstract::Autophosphorylated growth factor receptors provide binding sites for the src homology 2 domains of intracellular signaling molecules. In response to epidermal growth factor (EGF), the activated EGF receptor binds to a complex containing the signaling protein GRB2 and the Ras guanine nucleotide-releasing factor Sos, le...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.1.509

    authors: Li W,Nishimura R,Kashishian A,Batzer AG,Kim WJ,Cooper JA,Schlessinger J

    更新日期:1994-01-01 00:00:00

  • Identification of an octamer-binding site in the mouse kappa light-chain immunoglobulin enhancer.

    abstract::A 215-base-pair (bp) region of the mouse MOPC 41 kappa light-chain immunoglobulin gene enhancer has been analyzed for specific binding of lymphoid and nonlymphoid nuclear factors. Mobility shift assays with a series of overlapping DNA fragments have mapped DNA-binding sites for three unique factors. The B-cell-specifi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.10.4239

    authors: Currie RA,Roeder RG

    更新日期:1989-10-01 00:00:00

  • The trithorax group gene moira encodes a brahma-associated putative chromatin-remodeling factor in Drosophila melanogaster.

    abstract::The genes of the trithorax group (trxG) in Drosophila melanogaster are required to maintain the pattern of homeotic gene expression that is established early in embryogenesis by the transient expression of the segmentation genes. The precise role of each of the diverse trxG members and the functional relationships amo...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.2.1159

    authors: Crosby MA,Miller C,Alon T,Watson KL,Verrijzer CP,Goldman-Levi R,Zak NB

    更新日期:1999-02-01 00:00:00

  • The LIM protein Ajuba regulates phosphatidylinositol 4,5-bisphosphate levels in migrating cells through an interaction with and activation of PIPKI alpha.

    abstract::The phosphoinositide phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] regulates the activity of many actin-binding proteins and as such is an important modulator of cytoskeleton organization during cell migration, for example. In migrating cells actin remodeling is tightly regulated and localized; therefore, how the ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.10.3956-3966.2005

    authors: Kisseleva M,Feng Y,Ward M,Song C,Anderson RA,Longmore GD

    更新日期:2005-05-01 00:00:00