Abstract:
:Using a proteomics screen, we have identified the methyltransferase G9a as an interacting partner of the hematopoietic activator NF-E2. We show that G9a is recruited to the beta-globin locus in a NF-E2-dependent manner and spreads over the entire locus. While G9a is often regarded as a corepressor, knocking down this protein in differentiating adult erythroid cells leads to repression of the adult beta(maj) globin gene and aberrant reactivation of the embryonic beta-like globin gene E(y). While in adult cells G9a maintains E(y) in a repressed state via dimethylation of histone H3 at lysines 9 and 27, it activates beta(maj) transcription in a methyltransferase-independent manner. Interestingly, the demethylase UTX is recruited to the beta(maj) (but not the E(y)) promoter where it antagonizes G9a-dependent H3K27 dimethylation. Collectively, these results reveal a dual role for G9a in maintaining proper expression (both repression and activation) of the beta-globin genes in differentiating adult erythroid cells.
journal_name
Proc Natl Acad Sci U S Aauthors
Chaturvedi CP,Hosey AM,Palii C,Perez-Iratxeta C,Nakatani Y,Ranish JA,Dilworth FJ,Brand Mdoi
10.1073/pnas.0906769106subject
Has Abstractpub_date
2009-10-27 00:00:00pages
18303-8issue
43eissn
0027-8424issn
1091-6490pii
0906769106journal_volume
106pub_type
杂志文章abstract::Predicting the timing of upcoming events is critical for successful interaction in a dynamic world, and is recognized as a key computation for attentional orienting. Temporal predictions can be formed when recent events define a rhythmic structure, as well as in aperiodic streams or even in isolation, when a specified...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1810596115
更新日期:2018-11-27 00:00:00
abstract::A method is presented for variational calculation of the energy and the spin densities derived from a single-determinant wavefunction. Sum and difference coordinates [unk]R = (1/2)([unk]r(1) + [unk]r(1)) and [unk]r = [unk]r(1) - [unk]r(1) are introduced, and the density matrix P([unk]r(1),[unk]r(1)) is expanded in par...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.11.6293
更新日期:1980-11-01 00:00:00
abstract::Early members of the dinosaur-pterosaur clade Ornithodira are very rare in the fossil record, obscuring our understanding of the origins of this important group. Here, we describe an early ornithodiran (Kongonaphon kely gen. et sp. nov.) from the Mid-to-Upper Triassic of Madagascar that represents one of the smallest ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1916631117
更新日期:2020-07-28 00:00:00
abstract::Development of in vitro resistance to HN2 (also called mustargen or mechlorethamine hydrochloride), N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU), and cisplatin [cis-diamminedichloroplatinum(II)] was achieved in two human cell lines, the Raji/Burkitt lymphoma and a squamous cell carcinoma of the tongue. A 10- to 20-fol...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.7.2158
更新日期:1985-04-01 00:00:00
abstract::Mineralogical processes taking place close to equilibrium, or with very slow kinetics, are difficult to quantify precisely. The determination of ultraslow dissolution/precipitation rates would reveal characteristic timing associated with these processes that are important at geological scale. We have designed an advan...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1105233108
更新日期:2011-09-20 00:00:00
abstract::An improved electron cloud bolometer is analyzed. In this device the cloud temperature is read out not via thermal noise induced by the electrons in a coupled LC circuit but via shift in their axial oscillation frequency in the Penning trap confining them. This shift occurs because as the electron cloud expands with i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.14.6308
更新日期:1994-07-05 00:00:00
abstract::The origin recognition complex (ORC) binds sites from which DNA replication is initiated. We address ORC binding selectivity in vivo by mapping ∼52,000 ORC2 binding sites throughout the human genome. The ORC binding profile is broader than those of sequence-specific transcription factors, suggesting that ORC is not bo...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1609060113
更新日期:2016-08-16 00:00:00
abstract::We have compared chicken erythrocyte linker histones H1 and H5 binding to a synthetic four-way DNA junction. Each histone binds to form a single complex, with an affinity which permits competition against a large excess of linear duplex DNA. The affinity of H5 is higher than that of H1. The globular domain from either...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.9.3525
更新日期:1994-04-26 00:00:00
abstract::Whether Golgi enzymes remain localized within the Golgi or constitutively cycle through the endoplasmic reticulum (ER) is unclear, yet is important for understanding Golgi dependence on the ER. Here, we demonstrate that the previously reported inefficient ER trapping of Golgi enzymes in a rapamycin-based assay results...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1520957112
更新日期:2015-12-08 00:00:00
abstract::SUMO, a small ubiquitin-related modifier, is known to covalently attach to a number of nuclear regulatory proteins such as p53, IkappaB, promyelocytic leukemia protein and c-Jun. The sumoylation reaction is catalyzed by the SUMO protease, which exposes the C-terminal active glycine residue of the nascent SUMO, the het...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0402889101
更新日期:2004-06-08 00:00:00
abstract::Previous studies have shown that DNA methyltransferase (Dnmt) 1 is required for maintenance of bulk DNA methylation and is essential for mouse development. However, somatic disruption of DNMT1 in the human cancer cell line HCT116 was not lethal and caused only minor decreases in methylation. Here, we report the identi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0604602103
更新日期:2006-09-19 00:00:00
abstract::Protein functions require conformational motions. We show here that the dominant conformational motions are slaved by the hydration shell and the bulk solvent. The protein contributes the structure necessary for function. We formulate a model that is based on experiments, insights from the physics of glass-forming liq...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0900336106
更新日期:2009-03-31 00:00:00
abstract::The stability of an immunogen against enzymatic degradation is considered an important factor for the design of synthetic vaccines. For our studies, we have selected an epitope from the tandem-repeat unit of the high-molecular-weight MUC2 mucin glycoprotein, which can be underglycosylated in case of colon cancer. In t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0407677102
更新日期:2005-01-11 00:00:00
abstract::HLA-I molecules play a central role in antigen presentation. They typically bind 9- to 12-mer peptides, and their canonical binding mode involves anchor residues at the second and last positions of their ligands. To investigate potential noncanonical binding modes, we collected in-depth and accurate HLA peptidomics da...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1717277115
更新日期:2018-05-15 00:00:00
abstract::The capacity of a so-called male recombination (MR) chromosome in Drosophila melanogaster to generate mutations at 14 X-chromosome loci specifying visible phenotypes was investigated. Appreciable increases in mutation were found at three loci y, sn, and ras. Tests of represnetative mutants generated at each locus esta...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.8.3490
更新日期:1977-08-01 00:00:00
abstract::Protein kinase C (PKC) and Syk protein tyrosine kinase play critical roles in immune cell activation including that through the high-affinity IgE receptor, FcepsilonRI. Mechanisms by which PKC activation leads to the activation of Ras, a family of GTPases essential for immune cell activation, have been elusive. We pre...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1633695100
更新日期:2003-08-05 00:00:00
abstract::A major problem facing the effective treatment of patients with cancer is how to get the specific antitumor agent into every tumor cell. In this report we describe the use of a strategy that, by using retroviral vectors encoding a truncated human CD5 cDNA, allows the selection of only the infected cells, and we show t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.24.13239
更新日期:1997-11-25 00:00:00
abstract::The mechanisms regulating expression of mouse mammary tumor virus (MMTV)-encoded superantigens from the viral sag gene are largely unknown, due to problems with detection and quantification of these low-abundance proteins. To study the expression and regulation of the MMTV sag gene, we have developed a sensitive and q...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.20.9293
更新日期:1995-09-26 00:00:00
abstract::Estrogen signaling occurs through at least two distinct molecular pathways: (i) direct binding of liganded estrogen receptors (ERs) to estrogen-responsive DNA elements (EREs) (the "ER/ERE pathway") and (ii) indirect recruitment of liganded ERs to activating protein-1 (AP-1)-responsive DNA elements via heterodimers of ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0407113102
更新日期:2005-01-18 00:00:00
abstract::Gametocytes are nonreplicative sexual forms that mediate malaria transmission to a mosquito vector. They are generated from asexual blood-stage parasites that proliferate in the circulation. However, little is known about how this transition is genetically regulated. Here, we report that an Apetala2 (AP2) family trans...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1504389112
更新日期:2015-10-13 00:00:00
abstract::Stimulation of the region antero-ventral to the third cerebral ventricle (AV3V) by a cholinergic drug, carbachol, and lesions of the AV3V have been demonstrated in previous studies to either augment or decrease sodium excretion, respectively. Atrial natriuretic peptide (ANP) dramatically increases renal sodium excreti...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.23.9621
更新日期:1989-12-01 00:00:00
abstract::Adenosine triphosphate (ATP) is a regulatory molecule for many cell functions, both for intracellular and, perhaps less well known, extracellular functions. An important example of the latter involves red blood cells (RBCs), which help regulate blood pressure by releasing ATP as a vasodilatory signaling molecule in re...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0805779105
更新日期:2008-10-28 00:00:00
abstract::Chromatin condensation plays an important role in the regulation of gene expression. Recently, it was shown that the transcriptional activation of Hoxd genes during vertebrate digit development involves modifications in 3D interactions within and around the HoxD gene cluster. This reorganization follows a global trans...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1517972112
更新日期:2015-11-10 00:00:00
abstract::Transcriptional activation of cytochrome P450 (CYP) genes and various drug metabolizing enzymes by the prototypical inducer phenobarbital (PB) and many other drugs and chemicals is an adaptive response of the organism to exposure to xenobiotics. The response to PB is mediated by the nuclear receptor constitutive andro...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0610216104
更新日期:2007-01-16 00:00:00
abstract::The diradical form of thiol-activated neocarzinostatin chromophore resides in the minor groove of DNA, where it has access to hydrogen atoms at the C-5', C-1', and C-4' positions of deoxyribose on each strand. In a dodecamer oligodeoxyribonucleotide containing the sequence AGC.GCT, a bistranded lesion staggered two nu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.15.6706
更新日期:1992-08-01 00:00:00
abstract::Decomposition is a critical source of plant nutrients, and drives the largest flux of terrestrial C to the atmosphere. Decomposing soil organic matter typically contains litter from multiple plant species, yet we lack a mechanistic understanding of how species diversity influences decomposition processes. Here, we sho...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0805600105
更新日期:2008-12-16 00:00:00
abstract::Molecular diversity of ion channel structure and function underlies variability in electrical signaling in nerve, muscle, and nonexcitable cells. Regulation by variable auxiliary subunits is a major mechanism to generate tissue- or cell-specific diversity of ion channel function. Mammalian large-conductance, voltage- ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1205435109
更新日期:2012-05-15 00:00:00
abstract::A subclass of zinc finger proteins containing a unique protein motif called the positive regulatory (PR) domain has been described. The members include the PRDI-BF1/Blimp-1 protein, the Caenorhabditis elegans egl-43 and EVI1 gene products, and the retinoblastoma interacting protein RIZ. Here we describe a member of th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.19.10705
更新日期:1999-09-14 00:00:00
abstract::Morphine is one of the most prescribed and effective drugs used for the treatment of acute and chronic pain conditions. In addition to its central effects, morphine can also produce peripheral analgesia. However, the mechanisms underlying this peripheral action of morphine have not yet been fully elucidated. Here, we ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0914733107
更新日期:2010-03-02 00:00:00
abstract::Direct visualization of genomic loci in the 3D nucleus is important for understanding the spatial organization of the genome and its association with gene expression. Various DNA FISH methods have been developed in the past decades, all involving denaturing dsDNA and hybridizing fluorescent nucleic acid probes. Here w...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1515692112
更新日期:2015-09-22 00:00:00