Abstract:
:Gene activation requires alteration of chromatin structure to facilitate active transcription complex formation at a gene promoter. Nucleosome remodeling complexes and histone modifying complexes each play unique and interdependent roles in bringing about these changes. The role of distant enhancers in these structural alterations is not well understood. We studied nucleosome remodeling and covalent histone modification mediated by the beta-globin locus control region HS2 enhancer at nucleosome-level resolution throughout a 5.5-kb globin gene model locus in vivo in K562 cells. We compared the transcriptionally active locus to one in which HS2 was inactivated by mutations in the core NF-E2 sites. In contrast to inactive templates, nucleosomes were mobilized in discrete areas of the active locus, including the HS2 core and the proximal promoter. Large differences in restriction enzyme accessibility between the active and inactive templates were limited to the regions of nucleosome mobilization, which subsumed the DNase I hypersensitive sites. In contrast to this discrete pattern, histone H3 and H4 acetylation and H3 K4 methylation were elevated across the entire active locus, accompanied by depletion of linker histone H1. The coding region of the gene differed from the regulatory regions, demonstrating both nucleosome mobilization and histone hyperacetylation, but lacked differences in restriction enzyme accessibility between transcriptionally active and inactive genes. Thus, although the histone modification pattern we observe is consistent with the spreading of histone modifying activity from the distant enhancer, the pattern of nucleosome mobilization is more compatible with direct contact between an enhancer and promoter.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Kim A,Dean Adoi
10.1128/mcb.23.22.8099-8109.2003subject
Has Abstractpub_date
2003-11-01 00:00:00pages
8099-109issue
22eissn
0270-7306issn
1098-5549journal_volume
23pub_type
杂志文章abstract::Adipocytes constitute a major part of the bone marrow stroma in vivo and may play an active role in lymphohematopoiesis. Earlier studies had shown that the bone marrow stromal cell clone BMS2 was capable of adipocyte differentiation in vitro, in addition to its well-defined ability to support B lymphopoiesis. We now d...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.11.4587
更新日期:1989-11-01 00:00:00
abstract::Insulin stimulates glucose transport into fat and muscle cells by increasing the exocytic trafficking rate of the GLUT4 facilitative glucose transporter from intracellular stores to the plasma membrane. Delivery of GLUT4 to the plasma membrane is mediated by formation of functional SNARE complexes containing syntaxin4...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01203-13
更新日期:2014-04-01 00:00:00
abstract::Activation of multiple signaling pathways is required to trigger the full spectrum of in vitro and in vivo phenotypic traits associated with neoplastic transformation by oncogenic Ras. To determine which of these pathways are important for N-ras tumorigenesis in human cancer cells and also to investigate the possibili...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.24.9294-9306.2000
更新日期:2000-12-01 00:00:00
abstract::The cyclin-dependent kinase inhibitor p21/WAF1/CIP1 is an important regulator of cell cycle progression, senescence, and differentiation. Genotoxic stress leads to activation of the tumor suppressor p53 and subsequently to induction of p21 expression. Here we show that the tumor suppressor p53 cooperates with the tran...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.8.2669-2679.2003
更新日期:2003-04-01 00:00:00
abstract::GCN4 is a transcriptional activator of amino acid-biosynthetic genes in the yeast Saccharomyces cerevisiae. GCN2, a translational activator of GCN4 expression, contains a domain homologous to the catalytic subunit of eucaryotic protein kinases. Substitution of a highly conserved lysine residue in the kinase domain abo...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.6.2820
更新日期:1990-06-01 00:00:00
abstract::In the budding yeast Saccharomyces cerevisiae, Cdc37 is required for the productive formation of Cdc28-cyclin complexes. The cdc37-1 mutant arrests at Start with low levels of Cdc28 protein, which is predominantly unphosphorylated at Thr169, fails to bind cyclin, and has little protein kinase activity. We show here th...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.3.749-754.2000
更新日期:2000-02-01 00:00:00
abstract::Mammary epithelial cells (MECs) detached from the extracellular matrix (ECM) produce deleterious reactive oxygen species (ROS) and induce autophagy to survive. The coordination of such opposing responses likely dictates whether epithelial cells survive ECM detachment or undergo anoikis. Here, we demonstrate that the e...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.05164-11
更新日期:2011-09-01 00:00:00
abstract::SUMO conjugation has emerged as a dynamic process in regulating protein function. Here we identify estrogen receptor β (ERβ) to be a new target of SUMO-1. ERβ SUMO-1 modification occurs on a unique nonconsensus sumoylation motif which becomes fully competent upon phosphorylation of its contained serine residue, which ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.06624-11
更新日期:2012-07-01 00:00:00
abstract::We set up an alternative splicing system in vitro in which the relative amounts of two spliced RNAs, one containing and the other lacking a particular exon, were directly proportional to the length of an inverted repeat inserted into the flanking introns. We then used the system to measure the effect of intramolecular...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.9.3194
更新日期:1987-09-01 00:00:00
abstract::Ubiquitously expressed transcription factors play an integral role in establishing and regulating patterns of gene transcription. Common factor 1 (CF1) is a ubiquitously expressed DNA-binding protein previously identified in our laboratory. We show here that CF1 recognizes sites in several diverse transcription elemen...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.3.1765
更新日期:1991-03-01 00:00:00
abstract::RNA editing in higher-plant chloroplasts involves C-to-U conversions at specific sites. Although in vivo analyses have been performed, little is known about the biochemical aspects of chloroplast editing reactions. Here we improved our original in vitro system and devised a procedure for preparing active chloroplast e...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.19.6726-6734.2002
更新日期:2002-10-01 00:00:00
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::Histone H3 lysine 9 (H3K9) methylation has broad roles in transcriptional repression, gene silencing, maintenance of heterochromatin, and epigenetic inheritance of heterochromatin. Using Xenopus laevis oocytes, we have previously shown that targeting G9a, an H3K9 histone methyltransferase, to chromatin increases H3K9 ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00948-06
更新日期:2006-09-01 00:00:00
abstract::Lacrimo-auriculo-dento-digital (LADD) syndrome is characterized by abnormalities in lacrimal and salivary glands, in teeth, and in the distal limbs. Genetic studies have implicated heterozygous mutations in fibroblast growth factor 10 (FGF10) and in FGF receptor 2 (FGFR2) in LADD syndrome. However, it is not clear whe...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00544-07
更新日期:2007-10-01 00:00:00
abstract::While the normal human erbB-2 gene is potently transforming when overexpressed in NIH 3T3 cells, its rat homolog, the neu gene, seems to acquire transforming properties only upon alteration of its coding sequence. In this study, we compared the effects of different levels of expression of normal erbB-2 and neu in NIH ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.6.3247
更新日期:1990-06-01 00:00:00
abstract::The fibroblast integrin alpha11beta1 is a key receptor for fibrillar collagens. To study the potential function of alpha11 in vivo, we generated a null allele of the alpha11 gene. Integrin alpha11(-/-) mice are viable and fertile but display dwarfism with increased mortality, most probably due to severely defective in...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00041-07
更新日期:2007-06-01 00:00:00
abstract::Cse4p is a variant of histone H3 that has an essential role in chromosome segregation and centromere chromatin structure in budding yeast. Cse4p has a unique 135-amino-acid N terminus and a C-terminal histone-fold domain that is more than 60% identical to histone H3 and the mammalian centromere protein CENP-A. Cse4p a...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.9.6130
更新日期:1999-09-01 00:00:00
abstract::Two signals activate meiosis in yeast: starvation and expression of the a1 and alpha 2 products of the mating-type locus. Prior studies suggest that these signals stimulate expression of an activator of meiosis, the IME1 (inducer of meiosis) product. We have cloned a gene, IME2, with properties similar to those of IME...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.5.2142
更新日期:1989-05-01 00:00:00
abstract::Secretory proteins in eukaryotic cells are transported to the cell surface via the endoplasmic reticulum (ER) and the Golgi apparatus by membrane-bounded vesicles. We screened a collection of temperature-sensitive mutants of Saccharomyces cerevisiae for defects in ER-to-Golgi transport. Two of the genes identified in ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.12.7139
更新日期:1998-12-01 00:00:00
abstract::The SMRT corepressor complex participates in transcriptional repression by a diverse array of vertebrate transcription factors. The ability to recruit SMRT appears to play a crucial role in leukemogenesis by the PML-retinoic acid receptor alpha (RARalpha) oncoprotein, an aberrant nuclear hormone receptor implicated in...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.21.7172-7182.2001
更新日期:2001-11-01 00:00:00
abstract::The RNA binding protein CPEB (cytoplasmic polyadenylation element binding) regulates cytoplasmic polyadenylation and translation in germ cells and the brain. In neurons, CPEB is detected at postsynaptic sites, as well as in the cell body. The related CPEB3 protein also regulates translation in neurons, albeit probably...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00716-10
更新日期:2010-12-01 00:00:00
abstract::Polyamines critically regulate all mammalian cell growth and proliferation by mechanisms such as the repression of growth-inhibitory proteins, including JunD. Decreasing the levels of cellular polyamines stabilizes JunD mRNA without affecting its transcription, but the exact mechanism whereby polyamines regulate JunD ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00807-10
更新日期:2010-11-01 00:00:00
abstract::Infection of mouse fibroblasts by wild-type polyomavirus results in increased phosphorylation of ribosomal protein S6 (D.A. Talmage, J. Blenis, and T.L. Benjamin, Mol. Cell. Biol. 8:2309-2315, 1988). Here we identify pp70 S6 kinase (pp70S6K) as a target for signal transduction events leading from polyomavirus middle t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.6.2728
更新日期:1996-06-01 00:00:00
abstract::Transfection of a plasmid encoding the Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) gene confers resistance to the antiproliferative effect of alpha interferon (IFN-alpha) in EBV-negative U968 cells (P. Aman and A. von Gabain, EMBO J. 9:147-152, 1990). We studied the expression of IFN-stimulated genes (ISGs) in ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.11.4930
更新日期:1992-11-01 00:00:00
abstract::Aromatic aminotransferase II, product of the ARO9 gene, catalyzes the first step of tryptophan, phenylalanine, and tyrosine catabolism in Saccharomyces cerevisiae. ARO9 expression is under the dual control of specific induction and nitrogen source regulation. We have here identified UASaro, a 36-bp upstream element ne...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.5.3360
更新日期:1999-05-01 00:00:00
abstract::The interaction of Prep1 and Pbx homeodomain transcription factors regulates their activity, nuclear localization, and likely, function in development. To understand the in vivo role of Prep1, we have analyzed an embryonic lethal hypomorphic mutant mouse (Prep1(i/i)). Prep1(i/i) embryos die at embryonic day 17.5 (E17....
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00313-06
更新日期:2006-08-01 00:00:00
abstract::The myeloperoxidase (MPO) and neutrophil elastase genes are expressed specifically in immature myeloid cells. The integrity of a polyomavirus enhancer core sequence, 5'-AACCACA-3', is critical to the activity of the murine MPO proximal enhancer. This element binds two species, myeloid nuclear factors 1 alpha and 1 bet...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.8.5558
更新日期:1994-08-01 00:00:00
abstract::The basic leucine zipper transcription factor, CCAAT/enhancer binding protein alpha (C/EBPalpha), is abundantly expressed in keratinocytes of the skin; however, its function in skin is poorly characterized. UVB radiation is responsible for the majority of human skin cancers. In response to UVB-induced DNA damage, kera...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.24.10650-10660.2004
更新日期:2004-12-01 00:00:00
abstract::Repetitive DNA sequences have been implicated in the mediation of DNA rearrangement in mammalian cells. We have tested this hypothesis by using a dihydrofolate reductase (DHFR) expression vector into which candidate sequences were inserted. DHFR- Chinese hamster ovary (CHO) cells were transfected with this vector, the...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.9.3611
更新日期:1988-09-01 00:00:00
abstract::R-loops have been described in vivo at the immunoglobulin class switch sequences and at prokaryotic and mitochondrial origins of replication. However, the biochemical mechanism and determinants of R-loop formation are unclear. We find that R-loop formation is nearly eliminated when RNase T(1) is added during transcrip...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01251-07
更新日期:2008-01-01 00:00:00