Abstract:
:Alternative mRNA splicing is an important means of diversifying function in higher eukaryotes. Notably, both NCoR and SMRT corepressors are subject to alternative mRNA splicing, yielding a series of distinct corepressor variants with highly divergent functions. Normal adipogenesis is associated with a switch in corepressor splicing from NCoRω to NCoRδ, which appears to help regulate this differentiation process. We report here that mimicking this development switch in mice by a splice-specific whole-animal ablation of NCoRω is very different from a whole-animal or tissue-specific total NCoR knockout and produces significantly enhanced weight gain on a high-fat diet. Surprisingly, NCoRω(-/-) mice are protected against diet-induced glucose intolerance despite enhanced adiposity and the presence of multiple additional, prodiabetic phenotypic changes. Our results indicate that the change in NCoR splicing during normal development both helps drive normal adipocyte differentiation and plays a key role in determining a metabolically appropriate storage of excess calories. We also conclude that whole-gene "knockouts" fail to reveal how important gene products are customized, tailored, and adapted through alternative mRNA splicing and thus do not reveal all the functions of the protein products of that gene.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Goodson ML,Young BM,Snyder CA,Schroeder AC,Privalsky MLdoi
10.1128/MCB.00554-14subject
Has Abstractpub_date
2014-11-15 00:00:00pages
4104-14issue
22eissn
0270-7306issn
1098-5549pii
MCB.00554-14journal_volume
34pub_type
杂志文章abstract::The complete nucleotide sequence of a genomic clone encoding the mouse skeletal alpha-actin gene has been determined. This single-copy gene codes for a protein identical in primary sequence to the rabbit skeletal alpha-actin. It has a large intron in the 5'-untranslated region 12 nucleotides upstream from the initiato...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.1.15
更新日期:1986-01-01 00:00:00
abstract::We show that expression of p57(Kip2), a potent tight-binding inhibitor of several G(1) cyclin-cyclin-dependent kinase (Cdk) complexes, increases markedly during C2C12 myoblast differentiation. We examined the effect of p57(Kip2) on the activity of the transcription factor MyoD. In transient transfection assays, transc...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.11.7621
更新日期:1999-11-01 00:00:00
abstract::Activation of adult myoblasts called satellite cells during muscle degeneration is an important aspect of muscle regeneration. Satellite cells are believed to be the only myogenic stem cells in adult skeletal muscle and the source of regenerating muscle fibers. Upon activation, satellite cells proliferate, migrate to ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.9.5550
更新日期:1997-09-01 00:00:00
abstract::Cks proteins associate with cyclin-dependent kinases and have therefore been assumed to play a direct role in cell cycle regulation. Mammals have two paralogs, Cks1 and Cks2, and individually deleting the gene encoding either in the mouse has previously been shown not to impact viability. In this study we show that si...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01833-07
更新日期:2008-09-01 00:00:00
abstract::The SLP-76 family of immune cell-specific adaptors is composed of three distinct members named SLP-76, Blnk, and Clnk. They have been implicated in the signaling pathways coupled to immunoreceptors such as the antigen receptors and Fc receptors. Previous studies using gene-targeted mice and deficient cell lines showed...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.13.6067-6075.2004
更新日期:2004-07-01 00:00:00
abstract::ADR1 is a yeast transcription factor that contains two zinc fingers of the Cys-2-His-2 (C2H2) class. Mutations that change the specificity of DNA binding of ADR1 to its target site, upstream activation sequence 1 (UAS1), have been identified at three positions in the first zinc finger. Mutations Arg-115 to Gln, His-11...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.6.2784
更新日期:1992-06-01 00:00:00
abstract::Scaffold proteins have been established as important mediators of signal transduction specificity. The insulin receptor substrate (IRS) proteins represent a critical group of scaffold proteins that are required for signal transduction by the insulin receptor, including the activation of phosphatidylinositol 3 kinase. ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00155-09
更新日期:2009-09-01 00:00:00
abstract::The influence of transcription on homologous intrachromosomal recombination between direct and inverted repeats has been examined by using Chinese hamster ovary cells. Recombination was monitored between two integrated neomycin (neo) genes, including one silent allele and a second allele regulated by the inducible mou...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.12.5311
更新日期:1992-12-01 00:00:00
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
更新日期:1999-07-01 00:00:00
abstract::Microtubules in yeast are essential components of the mitotic and meiotic spindles and are essential for nuclear movement during cell division and mating. The relative importance in these processes of the two divergent alpha-tubulin genes of the budding yeast Saccharomyces cerevisiae, TUB1 and TUB3, was examined throu...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.11.3722
更新日期:1986-11-01 00:00:00
abstract::To characterize further the regulatory mechanism modulating the expression of the Saccharomyces cerevisiae ARG3 gene, i.e., the specific repression by arginine and the general amino acid control, we analyzed by deletion the region upstream of that gene, determined the nucleotide sequence of operator-constitutive-like ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.11.3139
更新日期:1985-11-01 00:00:00
abstract::To investigate the role of myogenin in regulating acetylcholine receptor expression in adult muscle, this muscle-specific basic helix-loop-helix transcription factor was overexpressed in transgenic mice by using regulatory elements conferring strong expression confined to differentiated postmitotic muscle fibers. Many...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.12.7127
更新日期:1995-12-01 00:00:00
abstract::NIH 3T3 cells infected with Moloney murine leukemia virus (MoMLV) express high levels of virus-specific RNA. To inhibit replication of the virus, we stably introduced chimeric tRNA genes encoding antisense templates into NIH 3T3 cells via a retroviral vector. Efficient expression of hybrid tRNA-MoMLV antisense transcr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.12.6512
更新日期:1990-12-01 00:00:00
abstract::Numerous studies indirectly implicate Rac GTPases in cancer. To investigate if Rac3 contributes to normal or malignant cell function, we generated rac3 null mutants through gene targeting. These mice were viable, fertile, and lacked an obvious external phenotype. This shows Rac3 function is dispensable for embryonic d...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.13.5777-5785.2005
更新日期:2005-07-01 00:00:00
abstract::We have previously described an isolated kinetoplast system from Crithidia fasciculata capable of ATP-dependent replication of kinetoplast DNA minicircles (L. Birkenmeyer and D.S. Ray, J. Biol. Chem. 261: 2362-2368, 1986). We present here the identification of two new minicircle species observed in short pulse-labelin...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.1.169
更新日期:1989-01-01 00:00:00
abstract::By assessing the contribution of deregulated E2F activity to erythroid defects in Rb null mice, we have identified E2f-2 as being upregulated in end-stage red cells, where we show it is the major pRb-associated E2f and the predominant E2f detected at key target gene promoters. Consistent with its expression pattern, E...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01118-07
更新日期:2007-12-01 00:00:00
abstract::c-Myc promotes apoptosis by destabilizing mitochondrial integrity, leading to the release of proapoptotic effectors including holocytochrome c. Candidate mediators of c-Myc in this process are the proapoptotic members of the Bcl-2 family. We show here that fibroblasts lacking Bak remain susceptible to c-Myc-induced ap...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.17.6158-6169.2002
更新日期:2002-09-01 00:00:00
abstract::To understand the function of SPT13, a gene encoding a trans-acting factor involved in regulation of Ty-mediated gene expression, we have cloned and sequenced the gene. Our analysis revealed that SPT13 is the same gene as GAL11, a gene in which mutations cause reduced expression of some GAL4-regulated genes. Further a...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.12.5602
更新日期:1989-12-01 00:00:00
abstract::The accurate segregation of chromosomes requires the kinetochore, a complex protein machine that assembles onto centromeric DNA to mediate attachment of replicated sister chromatids to the mitotic spindle apparatus. This study reveals an important role for the yeast RSC ATP-dependent chromatin-remodeling complex at th...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.9.3202-3215.2003
更新日期:2003-05-01 00:00:00
abstract::X chromosome inactivation silences one of two X chromosomes in the mammalian female cell and is controlled by a binary switch that involves interactions between Xist and Tsix, a sense-antisense pair of noncoding genes. On the future active X chromosome, Tsix expression suppresses Xist upregulation, while on the future...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.7.2757-2769.2005
更新日期:2005-04-01 00:00:00
abstract::Recombination enhancer (RE) is essential for regulating donor preference during yeast mating type switching. In this study, by using minichromosome affinity purification (MAP) and mass spectrometry, we found that yeast Ku80p is associated with RE in MATa cells. Chromatin immunoprecipitation assays confirmed its occupa...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.19.8476-8485.2005
更新日期:2005-10-01 00:00:00
abstract::The Saccharomyces cerevisiae RAD18 gene is essential for postreplication repair but is not required for homologous recombination (HR), which is the major double-strand break (DSB) repair pathway in yeast. Accordingly, yeast rad18 mutants are tolerant of camptothecin (CPT), a topoisomerase I inhibitor, which induces DS...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01243-06
更新日期:2007-04-01 00:00:00
abstract::Drosophila virilis genomic DNA corresponding to the D. melanogaster embryonic lethal abnormal visual system (elav) locus was cloned. DNA sequence analysis of a 3.8-kb genomic piece allowed identification of (i) an open reading frame (ORF) with striking homology to the previously identified D. melanogaster ORF and (ii)...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.6.2994
更新日期:1991-06-01 00:00:00
abstract::TFIID, comprising the TATA box binding protein (TBP) and 13 TBP-associated factors (TAFs), plays a role in nucleation in the assembly of the RNA polymerase II preinitiation complexes on protein-encoding genes. TAFs are shared among other transcription regulatory complexes (e.g., SAGA, TBP-free TAF-containing complex [...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.10.4092-4104.2005
更新日期:2005-05-01 00:00:00
abstract::The products of c-fos and c-jun (Fos and Jun) function in gene regulation by interacting with the AP-1 binding site. Here we have examined the contribution of Fos and Jun toward transcriptional activity by using Fos and Jun polypeptides purified from Escherichia coli. Fos contained a transcriptional activation domain ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.10.5532
更新日期:1990-10-01 00:00:00
abstract::We describe here a new cell line, EL2, which spontaneously arose from primary rat embryo fibroblasts and has the distinctive property of being highly susceptible to a number of different transforming genes. The high susceptibility is expressed not only in high transformation frequencies but, most importantly, in an un...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.12.2925
更新日期:1984-12-01 00:00:00
abstract::The GGAs (Golgi-localized, gamma-ear-containing, ARF-binding proteins) are a family of multidomain adaptor proteins involved in protein sorting at the trans-Golgi network of eukaryotic cells. Here we present results from a functional characterization of the two Saccharomyces cerevisiae GGAs, Gga1p and Gga2p. We show t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.23.7981-7994.2001
更新日期:2001-12-01 00:00:00
abstract::There are five members of the RFX family of transcription factors in mammals. While RFX5 plays a well-defined role in the immune system, the functions of RFX1 to RFX4 remain largely unknown. We have generated mice with a deletion of the Rfx3 gene. RFX3-deficient mice exhibit frequent left-right (LR) asymmetry defects ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.10.4417-4427.2004
更新日期:2004-05-01 00:00:00
abstract::The tissue-specific expression of immunoglobulin genes can be partially explained by a requirement for activating factors found only in B lymphocytes and their derivatives. However, loss of immunoglobulin expression upon fusion of an immunoglobulin-producing myeloma cell with a T lymphoma cell (BW5147) or fibroblast (...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.5.1932
更新日期:1988-05-01 00:00:00
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
更新日期:1999-07-01 00:00:00