Abstract:
:The association of transcription corepressors SMRT and N-CoR with retinoid and thyroid receptors results in suppression of basal transcriptional activity. A key event in nuclear receptor signaling is the hormone-dependent release of corepressor and the recruitment of coactivator. Biochemical and structural studies have identified a universal motif in coactivator proteins that mediates association with receptor LBDs. We report here the identity of complementary acting signature motifs in SMRT and N-CoR that are sufficient for receptor binding and ligand-induced release. Interestingly, the motif contains a hydrophobic core (PhixxPhiPhi) similar to that found in NR coactivators. Surprisingly, mutations in the amino acids that directly participate in coactivator binding disrupt the corepressor association. These results indicate a direct mechanistic link between activation and repression via competition for a common or at least partially overlapping binding site.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Nagy L,Kao HY,Love JD,Li C,Banayo E,Gooch JT,Krishna V,Chatterjee K,Evans RM,Schwabe JWdoi
10.1101/gad.13.24.3209subject
Has Abstractpub_date
1999-12-15 00:00:00pages
3209-16issue
24eissn
0890-9369issn
1549-5477journal_volume
13pub_type
杂志文章abstract::Two broad gene classes are distinguished within multicellular organisms: cell type-specific genes, which confer particular cellular properties, and ubiquitous genes that support general cellular functions. However, certain so-called ubiquitous genes show functionally relevant cell type-specific repression. How such re...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.287904.116
更新日期:2016-09-15 00:00:00
abstract::The release of Agrin by motoneurons activates the muscle-specific receptor tyrosine kinase (MuSK) as the main organizer of subsynaptic specializations at the neuromuscular junction. MuSK downstream signaling is largely undefined. Here we show that protein kinase CK2 interacts and colocalizes with MuSK at post-synaptic...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.375206
更新日期:2006-07-01 00:00:00
abstract::The organizer region, or dorsal blastopore lip, plays a central role in the initiation of gastrulation and the formation of the body axis during Xenopus development. A similar process can also be induced in ectodermal explants by activin or by injection of activin mRNA into embryos. We have searched early embryo-speci...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.4.599
更新日期:1992-04-01 00:00:00
abstract::Known prions (infectious proteins) are self-propagating amyloids or conformationally altered proteins, but in theory an enzyme necessary for its own activation could also be a prion (or a gene composed of protein). We show that yeast protease B is such a prion, called [beta].[beta] is infectious, reversibly curable, a...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1115803
更新日期:2003-09-01 00:00:00
abstract::Our understanding of eukaryotic transcriptional activation mechanisms has been hampered by an inability to identify the direct in vivo targets of activator proteins, primarily because of lack of appropriate experimental methods. To circumvent this problem, we have developed a fluorescence resonance energy transfer (FR...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1148404
更新日期:2004-02-01 00:00:00
abstract::Alteration of nucleosomes by ATP-dependent remodeling complexes represents a critical step in the regulation of transcription. The human SWI/SNF (hSWI/SNF) family is composed of complexes that contain either Brg1 or hBrm as the central ATPase; however, these separate complexes have not been compared functionally. Here...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.872801
更新日期:2001-03-01 00:00:00
abstract::The distal appendages (DAPs) of centrioles have been proposed to anchor cilia to the plasma membrane, but their molecular composition, assembly, and exact function in ciliogenesis remain poorly understood. Using quantitative centrosome proteomics and superresolution microscopy, we identified five DAP components, inclu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.207043.112
更新日期:2013-01-15 00:00:00
abstract::Kinase suppressor of Ras (KSR) is a recently identified component of Ras-dependent signaling pathways. In this report, we show that murine KSR1 (mKSR1) cooperates with activated Ras to promote Xenopus oocyte maturation and cellular transformation and provide evidence that this cooperation occurs by accelerating mitoge...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.21.2684
更新日期:1996-11-01 00:00:00
abstract::Outward migration of epidermal progenitors occurs with induction of hundreds of differentiation genes, but the identities of all regulators required for this process are unknown. We used laser capture microdissection followed by RNA sequencing to identify calmodulin-like 5 (CALML5) as the most enriched gene in differe...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.267708.115
更新日期:2015-11-01 00:00:00
abstract::Binding of microRNA (miRNA) to mRNA within the RNA-induced silencing complex (RISC) leads to either translational inhibition or to destruction of the target mRNA. Both of these functions are executed by Argonaute 2 (Ago2). Using hematopoiesis in mice as a model system to study the physiological function of Ago2 in viv...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1565607
更新日期:2007-08-15 00:00:00
abstract::For all newborn mammals, mother's milk is the perfect nourishment, crucial for their postnatal development. Here we report that, unexpectedly, maternal western diet consumption in mice causes the production of toxic milk that contains excessive long chain and saturated fatty acids, which triggers ceramide accumulation...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.191031.112
更新日期:2012-06-15 00:00:00
abstract::The neurofibromatosis type II (NF2) tumor suppressor encodes a putative cytoskeletal associated protein, the loss of which leads to the development of Schwann cell tumors associated with NF2 in humans. The NF2 protein merlin belongs to the band 4.1 family of proteins that link membrane proteins to the cytoskeleton and...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.10.1253
更新日期:1997-05-15 00:00:00
abstract::The hair follicle undergoes a lifelong developmental cycle that depends on the integration between activating and inhibitory signals acting to regulate and guide the proliferation and differentiation of pluripotent epithelial stem cells. The effectors and mechanisms responsible for re-entry of quiescent telogen hair f...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.223172.113
更新日期:2013-06-15 00:00:00
abstract::The transcription cofactor MAL is regulated by free actin levels and thus by actin dynamics. MAL, together with its DNA-binding partner, SRF, is required for invasive cell migration and in experimental metastasis. Although MAL/SRF has many targets, we provide genetic evidence in both Drosophila and human cellular mode...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.237743.114
更新日期:2014-05-15 00:00:00
abstract::Genomic imprinting is essential for mammalian development. Recent studies have revealed that maternal histone H3 Lys27 trimethylation (H3K27me3) can mediate DNA methylation-independent genomic imprinting. However, the regulatory mechanisms and functions of this new imprinting mechanism are largely unknown. Here we dem...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.318675.118
更新日期:2018-12-01 00:00:00
abstract::Atypical teratoid rhabdoid tumors (ATRTs) are challenging pediatric brain cancers that are predominantly associated with inactivation of the gene SMARCB1, a conserved subunit of the chromatin remodeling BAF complex, which has known contributions to developmental processes. To identify potential interactions between SM...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.339978.120
更新日期:2020-10-01 00:00:00
abstract::The ability to initiate organs throughout the lifecycle is a unique feature of plant development that is executed by groups of stem cells called meristems. The balance between stem cell proliferation and organ initiation is carefully regulated and ensures that organs can be initiated in regular geometric patterns. To ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.208501
更新日期:2001-10-15 00:00:00
abstract::The Elongin BC complex was identified initially as a positive regulator of RNA polymerase II (Pol II) elongation factor Elongin A and subsequently as a component of the multiprotein von Hippel-Lindau (VHL) tumor suppressor complex, in which it participates in both tumor suppression and negative regulation of hypoxia-i...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.24.3872
更新日期:1998-12-15 00:00:00
abstract::Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) provides a unique opportunity to derive patient-specific stem cells with potential applications in tissue replacement therapies and without the ethical concerns of human embryonic stem cells (hESCs). However, cellular senescence, which c...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.173922.111
更新日期:2011-11-01 00:00:00
abstract::In the July 15, 2010, issue of Genes & Development, Yoon and colleagues (pp. 1507-1518) report that, in a siRNA knockdown survey of 6363 genes in mouse C2C12 cells, they discovered 150 genes that regulated mitochondrial biogenesis and bioenergetics. Many of these genes have been studied previously for their importance...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.1960210
更新日期:2010-08-01 00:00:00
abstract::SpoIIIE is an FtsK-related protein that transports the forespore chromosome across the Bacillus subtilis sporulation septum. We use membrane photobleaching and protoplast assays to demonstrate that SpoIIIE is required for septal membrane fission in the presence of trapped DNA, and that DNA is transported across separa...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1925210
更新日期:2010-06-01 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::The target gene(s) required for Myc-mediated tumorigenesis are still elusive. Here we show that while endogenous c-Myc is surprisingly dispensable for skin homeostasis and TPA-induced hyperplasia, c-Myc-deficient epidermis is resistant to Ras-mediated DMBA/TPAinduced tumorigenesis. This is mechanistically linked to p2...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.381206
更新日期:2006-08-01 00:00:00
abstract::Discrete sequence elements known as exonic splicing enhancers (ESEs) have been shown to influence both the efficiency of splicing and the profile of mature mRNAs in multicellular eukaryotes. While the existence of ESEs has not been demonstrated previously in unicellular eukaryotes, the factors known to recognize these...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1265905
更新日期:2005-01-15 00:00:00
abstract::Checkpoint genes maintain genomic stability by arresting cells after DNA damage. Many of these genes also control cell cycle events in unperturbed cells. By conducting a screen for checkpoint genes in zebrafish, we found that dtl/cdt2 is an essential component of the early, radiation-induced G2/M checkpoint. We subseq...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1482106
更新日期:2006-11-15 00:00:00
abstract::Fgf-10-deficient mice (Fgf-10(-/-)) were generated to determine the role(s) of Fgf-10 in vertebrate development. Limb bud initiation was abolished in Fgf-10(-/-) mice. Strikingly, Fgf-10(-/-) fetuses continued to develop until birth, despite the complete absence of both fore- and hindlimbs. Fgf-10 is necessary for api...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.20.3156
更新日期:1998-10-15 00:00:00
abstract::Antigenic stimulation of the B-cell receptor (BCR) is a central event in the immune response. In contrast, antigen bound to IgG negatively regulates signals from the BCR by cross-linking it to the inhibitory receptor FcgammaRIIB. Here we show that upon cross-linking of BCR or BCR with FcgammaRIIB, the rasGAP-associate...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-01-01 00:00:00
abstract::Nucleosomes are positioned in the presence of the yeast repressor alpha 2 in minichromosomes containing the alpha 2 operator and on the promoters of a-cell-specific genes regulated by alpha 2. To investigate the possibility that alpha 2 directs nucleosome position through an interaction with a component of the core pa...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.3.411
更新日期:1992-03-01 00:00:00
abstract::Human TFIIA activity is composed of three subunits (alpha, beta, gamma). Here we report the isolation of a human cDNA clone encoding the gamma-subunit and the reconstitution of TFIIA activity from recombinant polypeptides (holo-TFIIA). Protein-protein interaction analysis established that the beta and gamma subunits o...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.19.2336
更新日期:1994-10-01 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