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 bound or recruited to specific DNA sequences. Instead, ORC binds nonspecifically to open (DNase I-hypersensitive) regions containing active chromatin marks such as H3 acetylation and H3K4 methylation. ORC sites in early and late replicating regions have similar properties, but there are far more ORC sites in early replicating regions. This suggests that replication timing is due primarily to ORC density and stochastic firing of origins. Computational simulation of stochastic firing from identified ORC sites is in accord with replication timing data. Large genomic regions with a paucity of ORC sites are strongly associated with common fragile sites and recurrent deletions in cancers. We suggest that replication origins, replication timing, and replication-dependent chromosome breaks are determined primarily by the genomic distribution of activator proteins at enhancers and promoters. These activators recruit nucleosome-modifying complexes to create the appropriate chromatin structure that allows ORC binding and subsequent origin firing.
journal_name
Proc Natl Acad Sci U S Aauthors
Miotto B,Ji Z,Struhl Kdoi
10.1073/pnas.1609060113subject
Has Abstractpub_date
2016-08-16 00:00:00pages
E4810-9issue
33eissn
0027-8424issn
1091-6490pii
1609060113journal_volume
113pub_type
杂志文章abstract::Androgens and the androgen receptor (AR) play important roles in the testes. Previously we have shown that male total AR knockout (T-AR-/y) mice revealed incomplete germ cell development and lowered serum testosterone levels, which resulted in azoospermia and infertility. However, the consequences of AR loss in partic...
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.0608556103
更新日期:2006-11-21 00:00:00
abstract::Mammalian nervous system function involves billions of neurons which are interconnected in a multitude of neural circuits. Here we describe a genetic approach to chart neural circuits. By using an olfactory-specific promoter, we selectively expressed barley lectin in sensory neurons in the olfactory epithelium and vom...
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.96.6.3194
更新日期:1999-03-16 00:00:00
abstract::Protective immunity against human schistosome infection develops slowly, for reasons that are not yet fully understood. For many decades, researchers have attempted to infer properties of the immune response from epidemiological studies, with mathematical models frequently being used to bridge the gap between immunolo...
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.1121051109
更新日期:2012-08-14 00:00:00
abstract::We have cloned a member of the nuclear receptor superfamily. The cDNA was isolated from a rat liver library and encodes a protein of 446 aa with a predicted mass of 50 kDa. This clone (OR-1) shows no striking homology to any known member of the steroid/thyroid hormone receptor superfamily. The most related receptor is...
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.92.6.2096
更新日期:1995-03-14 00:00:00
abstract::Saccharomyces cerevisiae Hop2 and Mnd1 are abundant meiosisspecific chromosomal proteins, and mutations in the corresponding genes lead to defects in meiotic recombination and in homologous chromosome interactions during mid-prophase. Analysis of various double mutants suggests that HOP2, MND1, and DMC1 act in the sam...
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.0404195101
更新日期:2004-07-20 00:00:00
abstract::Kaposi's sarcoma-associated herpesvirus (KSHV), etiologically associated with Kaposi's sarcoma, uses integrins (α3β1, αVβ3, and αVβ5) and associated signaling to enter human dermal microvascular endothelial cells (HMVEC-d), an in vivo target of infection. KSHV infection activated c-Cbl, which induced the selective tra...
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.1119592109
更新日期:2012-05-08 00:00:00
abstract::A Poincaré resolution is given for the supersymmetric ring of brackets over a signed alphabet. As a consequence, a resolution is found for the ring of coordinates of the Grassmanian variety in projective space over any infinite field. ...
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.88.18.8087
更新日期:1991-09-15 00:00:00
abstract::The binding of a few molecules [1-6] of RNA bacteriophage coat protein to 1 molecule of RNA represses in vitro translation of the RNA synthetase cistron. Digestion of the complex, R17 coat protein-R17 RNA, by T1 RNase yields an RNA fragment bound to the coat protein. The nucleotide sequence of this fragment (59 residu...
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.69.10.3033
更新日期:1972-10-01 00:00:00
abstract::During the analysis of liver protein expression in the offspring of male mice irradiated with fission-spectrum neutrons, one offspring displayed a heritable 50% decrease in the abundance of two proteins. Homozygous mice lacking detectable quantities of these proteins were obtained through breeding. Characterization 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.91.24.11338
更新日期:1994-11-22 00:00:00
abstract::We have used the polymerase chain reaction (PCR) to amplify up to 22 kb of the beta-globin gene cluster from human genomic DNA and up to 42 kb from phaga lambda DNA. We have also amplified 91 human genomic inserts of 9-23 kb directly from recombinant lambda plaques. To do this, we increased pH, added glycerol and dime...
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.91.12.5695
更新日期:1994-06-07 00:00:00
abstract::Effective therapies for most solid cancers, especially those that have progressed to metastasis, remain elusive because of inherent and acquired resistance of tumor cells to conventional treatments. Additionally, the effective therapeutic window for many protocols can be very narrow, frequently resulting in toxicity. ...
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.0700042104
更新日期:2007-02-27 00:00:00
abstract::Endothelial cells (ECs) not only are important for oxygen delivery but also act as a paracrine source for signals that determine the balance between tissue regeneration and fibrosis. Here we show that genetic inactivation of flow-induced transcription factor Krüppel-like factor 2 (KLF2) in ECs results in reduced liver...
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.1613392114
更新日期:2017-04-11 00:00:00
abstract::Astrocytes purified from primary cultures of neonatal rat cerebrum can now be grown in a synthetic medium supplemented with putrescine, prostaglandin F2 alpha, insulin, fibroblast growth factor, and hydrocortisone. These five supplements have a marked synergistic effect on growth when used in combination but have litt...
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.78.11.7205
更新日期:1981-11-01 00:00:00
abstract::We present a unique proxy for the reconstruction of variation in precipitation over the Amazon: oxygen isotope ratios in annual rings in tropical cedar (Cedrela odorata). A century-long record from northern Bolivia shows that tree rings preserve the signal of oxygen isotopes in precipitation during the wet season, wit...
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.1205977109
更新日期:2012-10-16 00:00:00
abstract::Swainsonine, an indolizidine alkaloid, inhibits the processing of asparagine-linked glycoproteins in both cell-free extracts and animal cells in culture. Thus, in a liver particulate enzyme preparation, swainsonine at 0.1-1.0 microM inhibited the mannosidase that releases [3H]mannose from a high mannose glycopeptide b...
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.78.12.7393
更新日期:1981-12-01 00:00:00
abstract::The global demand for food could double in another 40 y owing to growth in the population and food consumption per capita. To meet the world's future food and sustainability needs for biofuels and renewable materials, the production of starch-rich cereals and cellulose-rich bioenergy plants must grow substantially whi...
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.1302420110
更新日期:2013-04-30 00:00:00
abstract::We describe a system for gene expression in plants based on the regulation mechanism of the yeast metallothionein (MT) gene. The system consists of two elements: (i) the yeast ace1 (activating copper-MT expression) gene encoding a transcription factor under control of the cauliflower mosaic virus (CaMV) 35S RNA promot...
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.90.10.4567
更新日期:1993-05-15 00:00:00
abstract::Hepatitis A virus (HAV) infects ∼1.4 million people annually and, although there is a vaccine, there are no licensed therapeutic drugs. HAV is unusually stable (making disinfection problematic) and little is known of how it enters cells and releases its RNA. Here we report a potent HAV-specific monoclonal antibody, R1...
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.1616502114
更新日期:2017-01-24 00:00:00
abstract::The DNA from tumors of Nicotiana glauca initiated by strains of Agrobacterium rhizogenes was shown to contain sequences that are homologous to the root-inducing (Ri) plasmid of the bacterium. Two independently established tumor lines contained a similar portion of the Ri-plasmid. The Ri-plasmid also hybridized to DNA ...
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.79.10.3193
更新日期:1982-05-01 00:00:00
abstract::A 24-amino acid residue peptide has been isolated from the Fc region of a human IgG1 myeloma protein. The peptide has associated with it the same ability to induce murine B cells to polyclonally secrete antibody as does the intact Fc fragment. Amino acid composition of the peptide indicates that on a mole/mole basis 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.79.17.5388
更新日期:1982-09-01 00:00:00
abstract::DNA photolyase is a pyrimidine-dimer repair enzyme that uses visible light. Photolyase generally contains two chromophore cofactors. One is a catalytic cofactor directly contributing to the repair of a pyrimidine-dimer. The other is a light-harvesting cofactor, which absorbs visible light and transfers energy to the c...
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.241371398
更新日期:2001-11-20 00:00:00
abstract::Cells are wrapped in inelastic membranes, yet they can sustain large mechanical strains by regulating their area. The area regulation in cells is achieved either by membrane folding or by membrane exo- and endocytosis. These processes involve complex morphological transformations of the cell membrane, i.e., invaginati...
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.1102358108
更新日期:2011-05-31 00:00:00
abstract::The key enzyme for transcription of protein-encoding genes in eukaryotes is RNA polymerase II (RNAPII). The recruitment of this enzyme during transcription initiation and its passage along the template during transcription elongation is regulated through the association and dissociation of several complexes. Elongator...
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.0502600102
更新日期:2005-05-24 00:00:00
abstract::Plasma growth hormone (GH) profiles are sexually differentiated in many species and regulate the sex-dependence of peripubescent growth rates and liver function, including steroid hydroxylase cytochrome P450 expression, by mechanisms that are poorly understood. By use of an external pump to deliver to hypophysectomize...
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.88.15.6868
更新日期:1991-08-01 00:00:00
abstract::Interleukin 2 (IL-2) plays a critical role in the growth and differentiation of lymphoid cells. The IL-2 signal is delivered intracellularly by the IL-2 receptor beta chain (IL-2R beta); however, the mechanism by which the signal reaches the nucleus remains unclear. In this study, we demonstrate the rapid activation o...
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.89.6.2022
更新日期:1992-03-15 00:00:00
abstract::We present molecular dating analyses for land plants that incorporate 33 fossil calibrations, permit rates of molecular evolution to be uncorrelated across the tree, and take into account uncertainties in phylogenetic relationships and the fossil record. We attached a prior probability to each fossil-based minimum age...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
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更新日期:2010-03-30 00:00:00
abstract::Adult workers in honeybee (Apis mellifera) colonies exhibit plasticity in hormonally regulated, age-based division of labor by altering their pattern of behavioral development in response to changes in colony conditions. One form of this plasticity is precocious development: levels of juvenile hormone increase prematu...
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.89.24.11726
更新日期:1992-12-15 00:00:00
abstract::The family of WD40-repeat (WDR) proteins is one of the largest in eukaryotes, but little is known about their function in brain development. Among 26 WDR genes assessed, we found 7 displaying a major impact in neuronal morphology when inactivated in mice. Remarkably, all seven genes showed corpus callosum defects, inc...
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.1713625114
更新日期:2017-10-31 00:00:00
abstract::Biomass burning drives changes in greenhouse gases, climate-forcing aerosols, and global atmospheric chemistry. There is controversy about the magnitude and timing of changes in biomass burning emissions on millennial time scales from preindustrial to present and about the relative importance of climate change and hum...
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.1807172115
更新日期:2018-12-04 00:00:00
abstract::The complex biomechanical events associated with embryo development are investigated in vivo, by using femtosecond laser pulse-induced ablation combined with multimodal nonlinear microscopy. We demonstrate controlled intravital ablations preserving local cytoskeleton dynamics and resulting in the modulation of specifi...
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.0405316102
更新日期:2005-01-25 00:00:00