Abstract:
:The myogenic regulatory factor MyoD dimerizes with other positive and negative regulatory factors through a conserved region called the helix-loop-helix (HLH) domain. Using a non-DNA-binding MyoD mutant with a normal HLH domain as a dimerization competitor in gel mobility shift assays in conjunction with various MyoD HLH mutants, nonhydrophobic amino acids were identified in the HLH domain that contribute to dimerization specificity with E12. The assay detected subtle differences in dimerization activity among the mutant MyoD proteins that correlated with their ability to activate transcription in vivo, but this correlation was not apparent in the absence of competitor. The identification of such nonhydrophobic residues enabled us to predict the differences in dimerization affinity among the four vertebrate myogenic factors with E12. The experiments confirmed the prediction. Furthermore, a high-affinity homodimerizing analog of MyoD was designed by a single substitution at one of these residue positions. These experimental results were strengthened when they were analyzed in terms of the crystal structure for the Max bHLHZip domain homodimer. This analysis has allowed us to identify those residues that form charged residue pairs between the two HLH domains of MyoD and E12 and determine the dimerization specificity of the bHLH proteins.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Shirakata M,Friedman FK,Wei Q,Paterson BMdoi
10.1101/gad.7.12a.2456subject
Has Abstractpub_date
1993-12-01 00:00:00pages
2456-70issue
12Aeissn
0890-9369issn
1549-5477journal_volume
7pub_type
杂志文章abstract::Although Apc is well characterized as a tumor-suppressor gene in the intestine, the precise mechanism of this suppression remains to be defined. Using a novel inducible Ahcre transgenic line in conjunction with a loxP-flanked Apc allele we, show that loss of Apc acutely activates Wnt signaling through the nuclear accu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.287404
更新日期:2004-06-15 00:00:00
abstract::Transcriptional repressors play a key role in establishing localized patterns of gene expression in the early Drosophila embryo. Several different modes of repression have been implicated in previous studies, including competition and direct interference with the transcription complex. Here, we present evidence for "q...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.15.1829
更新日期:1994-08-01 00:00:00
abstract::Spindle checkpoint silencing is a critical step during mitosis that initiates chromosome segregation, yet surprisingly little is known about its mechanism. Protein phosphatase I (PP1) was shown recently to be a key player in this process, and in this issue of Genes & Deverlopment, Akiyoshi and colleagues (pp. 2887-289...
journal_title:Genes & development
pub_type: 评论,杂志文章,评审
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更新日期:2009-12-15 00:00:00
abstract::Eukaryotic genomes encode large families of deubiquitinating enzymes (DUBs). Genetic data suggest that Fat facets (Faf), a Drosophila DUB essential for patterning the compound eye, might have a novel regulatory function; Faf might reverse the ubiquitination of a specific substrate, thereby preventing proteasomal degra...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.961502
更新日期:2002-02-01 00:00:00
abstract::In Saccharomyces cerevisiae, gene silencing at the HMR and HML loci is normally dependent on Sir2p, Sir3p, and Sir4p, which are structural components of silenced chromatin. Sir2p is a NAD+-dependent histone deacetylase required for silencing. Silencing can be restored in cells lacking Sir proteins by a dominant mutati...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.873601
更新日期:2001-04-15 00:00:00
abstract::How muscle diversity is generated in the vertebrate body is poorly understood. In the limb, dorsal and ventral muscle masses constitute the first myogenic diversification, as each gives rise to distinct muscles. Myogenesis initiates after muscle precursor cells (MPCs) have migrated from the somites to the limb bud and...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.187807.112
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abstract::Protection of the stalled replication fork is crucial for responding to replication stress and minimizing its impact on chromosome instability, thus preventing diseases, including cancer. We found a new component, Abro1, in the protection of stalled replication fork integrity. Abro1 deficiency results in increased chr...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.299172.117
更新日期:2017-07-15 00:00:00
abstract::The Drosophila brain tumor (brat) gene encodes a member of the conserved NHL family of proteins, which appear to regulate differentiation and growth in a variety of organisms. One of the founding family members, Caenorhabditis elegans LIN-41, is thought to control posttranscriptional gene expression. However, the mech...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.870801
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abstract::The mechanisms by which homeoproteins bind selectively to target genes in vivo have long remained unresolved. Here we report that PIAS1 confers DNA-binding specificity on the Msx1 homeoprotein by regulating its subnuclear localization and proximity to target genes. We demonstrate that the interaction of Msx1 with PIAS...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1392006
更新日期:2006-04-01 00:00:00
abstract::The mottler of white (mw) locus has been determined to interact with alleles of the white (w) eye color locus which are a subset of the transposable element insertion mutants. The transposable elements belong to six different types, including copia, and are located at several sites within the w gene. Three X-ray-induc...
journal_title:Genes & development
pub_type: 杂志文章
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更新日期:1989-01-01 00:00:00
abstract::The generation of neurons by progenitor cells involves the tight coordination of multiple cellular activities, including cell cycle exit, initiation of neuronal differentiation, and cell migration. The mechanisms that integrate these different events into a coherent developmental program are not well understood. Here ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.377106
更新日期:2006-06-01 00:00:00
abstract::Eukaryotic chromosomes reach their stable rod-shaped appearance in mitosis in a reaction dependent on the evolutionarily conserved condensin complex. Little is known about how and where condensin associates with chromosomes. Here, we analyze condensin binding to budding yeast chromosomes using high-resolution oligonuc...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1675708
更新日期:2008-08-15 00:00:00
abstract::The reelin (reln) and disabled 1 (dab1) genes both ensure correct neuronal positioning during brain development. We have found that the intracellular Dab1 protein receives a tyrosine phosphorylation signal from extracellular Reln protein. Genetic analysis shows that reln function depends on dab1, and vice versa, as ex...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.6.643
更新日期:1999-03-15 00:00:00
abstract::IkappaB kinases (IKKs) IKK1 and IKK2 are two putative IkappaBalpha kinases involved in NF-kappaB activation. To examine the in vivo functions of IKK1, we generated IKK1-deficient mice. The mutant mice are perinatally lethal and exhibit a wide range of developmental defects. Newborn mutant mice have shiny, taut, and st...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.10.1322
更新日期:1999-05-15 00:00:00
abstract::Eph receptors and ephrin ligands are key players in many developmental processes including embryo patterning, angiogenesis, and axon guidance. Eph/ephrin interactions lead to the generation of a bidirectional signal, in which both the Eph receptors and the ephrins activate downstream signaling cascades simultaneously....
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1171704
更新日期:2004-03-01 00:00:00
abstract::Although progesterone has been recognized as essential for the establishment and maintenance of pregnancy, this steroid hormone has been recently implicated to have a functional role in a number of other reproductive events. The physiological effects of progesterone are mediated by the progesterone receptor (PR), a me...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.18.2266
更新日期:1995-09-15 00:00:00
abstract::Transcriptional profiling is a powerful approach for understanding development and disease. Current cell type-specific RNA purification methods have limitations, including cell dissociation trauma or inability to identify all RNA species. Here, we describe "mouse thiouracil (TU) tagging," a genetic and chemical inters...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.205278.112
更新日期:2013-01-01 00:00:00
abstract::Erasure and subsequent reinstatement of DNA methylation in the germline, especially at imprinted CpG islands (CGIs), is crucial to embryogenesis in mammals. The mechanisms underlying DNA methylation establishment remain poorly understood, but a number of post-translational modifications of histones are implicated in a...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.271353.115
更新日期:2015-12-01 00:00:00
abstract::In recent years several new mouse models for lung cancer have been described. These include models for both non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Tumorigenesis in these conditional mouse tumor models can be initiated in adult mice through Cre-recombinase-induced activation of oncogenic ...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1284505
更新日期:2005-03-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.604610
更新日期:2010-11-01 00:00:00
abstract::Start sites of DNA replication are marked by the origin recognition complex (ORC), which coordinates Mcm2-7 helicase loading to form the prereplicative complex (pre-RC). Although pre-RC assembly is well characterized in vitro, the process is poorly understood within the local chromatin environment surrounding replicat...
journal_title:Genes & development
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abstract::RNAi has revolutionized reverse genetics; however, RNAi is not necessarily ubiquitous or constitutive. Lund and colleagues (pp. 1121-1131) show that microRNA (miRNA) effector Argonautes (Agos) are limiting and easily saturated during early Xenopus embryogenesis. Moreover, this stage is devoid of slicing capacity. Supp...
journal_title:Genes & development
pub_type: 评论,杂志文章
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更新日期:2011-06-01 00:00:00
abstract::The cooperation of oncogenes in the transformation of primary rat Schwann cells is a strikingly synergistic process. We have explored the molecular mechanisms involved. Activation of an inducible Raf kinase results in morphologically transformed cells that are arrested in G1 via the induction of p21(CiP1) and subseque...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.5.663
更新日期:1997-03-01 00:00:00
abstract::Estrogen receptor α (ER) is the major driver of ∼75% of breast cancers, and multiple ER targeting drugs are routinely used clinically to treat patients with ER+ breast cancer. However, many patients relapse on these targeted therapies and ultimately develop metastatic and incurable disease, and understanding the mecha...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.316646.118
更新日期:2018-09-01 00:00:00
abstract::The Neurospora crassa clock-controlled gene (ccg-2) is transcriptionally activated by the circadian clock in a time-of-day-specific manner. Transcript and sequence analyses of ccg-2 reveal that the predicted Ccg-2 polypeptide bears significant similarity to a class of low-molecular-weight, cysteine-rich, hydrophobic p...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.12a.2382
更新日期:1992-12-01 00:00:00
abstract::We report a new role for Wnt signaling in the vertebrate embryo: the induction of neural tissue from ectoderm. Early expression of mouse wnt8, Xwnt8, beta-catenin, or dominant-negative GSK3 induces the expression of neural-specific markers and inhibits the expression of Bmp4 in Xenopus ectoderm. We show that Wnt8, but...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.23.3149
更新日期:1999-12-01 00:00:00
abstract::During Drosophila embryogenesis, ectodermal cells of the lateral epithelium stretch in a coordinated fashion to internalize the amnioserosa cells and close the embryo dorsally. This process, dorsal closure, requires two signaling pathways: the Drosophila Jun-amino-terminal kinase (DJNK) pathway and the Dpp pathway. We...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.13.1717
更新日期:1997-07-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:1993-04-01 00:00:00
abstract::Somitogenesis involves the segmentation of the paraxial mesoderm into units along the anteroposterior axis. Here we show a role for Eph and ephrin signaling in the patterning of presomitic mesoderm and formation of the somites. Ephrin-A-L1 and ephrin-B2 are expressed in an iterative manner in the developing somites an...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.19.3096
更新日期:1998-10-01 00:00:00
abstract::In mitosis, the spindle checkpoint protein Mad2 averts aneuploidy by delaying anaphase onset until chromosomes align. Here we show that depletion of Mad2 in meiosis I mouse oocytes induced an increased incidence of aneuploidy. Proteolysis of cyclin B and securin commenced earlier in Mad2-depleted oocytes, resulting in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.328105
更新日期:2005-01-15 00:00:00