Abstract:
:We report results showing that several gamma gene promoter elements participate in the developmental control of gamma-globin genes. Four gamma gene constructs with 5' truncated at -141, -201, -382, and -730 of the A gamma gene promoter linked to a micro locus control region (microLCR) cassette were used for production of transgenic mice and analysis of gamma gene expression during development. Mice carrying a microLCR -141 A gamma construct displayed downregulation of gamma gene expression in the adult stage of development, indicating that the proximal promoter contains elements participating in gamma gene silencing. Mice carrying a microLCR -201 A gamma or a microLCR -382 A gamma construct displayed high gamma gene expression in the fetal stage of development and complete loss of gamma gene downregulation in the adult stage, suggesting that the -141 to -201 gamma gene sequence contains elements which upregulate gamma gene expression and are dominant over the negative element 3' to -141. Extension of the promoter to -730 resulted in reappearance of gamma gene downregulation, suggesting that the -382 to -730 sequences contain an adult-stage-specific silencer. gamma gene expression in the microLCR -201 A gamma and the microLCR -382 A gamma transgenic mice was copy number dependent. All the microLCR -730 A gamma transgenic mice expressed gamma mRNA; however, gamma gene expression was copy number independent, indicating that levels of gamma gene expression were modulated by the surrounding chromatin. Our results suggest that multiple elements participate in gamma gene silencing. The findings in the microLCR-201 A gamma and microLCR -382 A gamma transgenic mice are interpreted to indicate that the LCR interacts not only with the minimal gamma gene promoter but also with sequences of the upstream promoter. We postulate that gamma gene downregulation is achieved when the interaction between LCR and the upstream promoter is disturbed by the silencer located in the -382 to -730 region. We propose that gamma gene silencing is achieved by the combined effect of negative elements located 3' to -141, the negative element located between -382 and -730, and the competition by the beta gene promoter during the adult stage of development.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Stamatoyannopoulos G,Josephson B,Zhang JW,Li Qdoi
10.1128/mcb.13.12.7636subject
Has Abstractpub_date
1993-12-01 00:00:00pages
7636-44issue
12eissn
0270-7306issn
1098-5549journal_volume
13pub_type
杂志文章abstract::Physiological cell deaths occur ubiquitously throughout biology and have common attributes, including apoptotic morphology with mitosis-like chromatin condensation and prelytic genome digestion. The fundamental question is whether a common mechanism of dying underlies these common hallmarks of death. Here we describe ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.5.2912
更新日期:1998-05-01 00:00:00
abstract::The transcriptional corepressor mSin3 is associated with histone deacetylases (HDACs) and is utilized by many DNA-binding transcriptional repressors. We have cloned and characterized a novel mSin3A-binding protein, SAP25. SAP25 binds to the PAH1 domain of mSin3A, associates with the mSin3A-HDAC complex in vivo, and re...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.4.1386-1397.2006
更新日期:2006-02-01 00:00:00
abstract::The sodium/iodide symporter (NIS) is a plasma membrane protein that mediates active iodide transport in thyroid and mammary cells. It is a prerequisite for radioiodide treatment of thyroid cancer and a promising diagnostic and therapeutic tool for breast cancer. We investigated the molecular mechanisms governing NIS e...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.18.7863-7877.2004
更新日期:2004-09-01 00:00:00
abstract::Ribosome biogenesis is a highly regulated process ensuring that cell growth (increase in biomass) is coordinated with cell proliferation. The formation of eukaryotic ribosomes is a multistep process initiated by the transcription and processing of rRNA in the nucleolus. Concomitant with this, several preribosomal part...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00358-10
更新日期:2010-09-01 00:00:00
abstract::We have analyzed the 5'-flanking region of one of the genes coding for the human acute-phase protein, serum amyloid A (SAA). We found that SAA mRNA could be increased fivefold in transfected cells by treatment with phorbol 12-myristate 13-acetate (PMA). To analyze this observation further, we placed a 265-base-pair 5'...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.5.1908
更新日期:1989-05-01 00:00:00
abstract::The homeo box gene even-skipped (eve) encodes a 376-amino-acid protein that binds with high affinity to sequences located near the 5' termini of the eve and en genes. The 5' en sites are A + T rich and contain copies of the 10-base-pair (bp) consensus sequence T-C-A-A-T-T-A-A-A-T. In contrast, the 5' eve sites are G +...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.11.4598
更新日期:1988-11-01 00:00:00
abstract::The selenoenzyme phospholipid hydroperoxide glutathione peroxidase (PHGPx) is regarded as the major molecular target of selenodeficiency in rodents, accounting for most of the histopathological and structural abnormalities of testicular tissue and male germ cells. PHGPx exists as a cytosolic form, mitochondrial form, ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.17.7637-7644.2005
更新日期:2005-09-01 00:00:00
abstract::Wrch-1, an atypical and transforming Rho GTPase, regulates cellular activities including proliferation and actin organization, but its functions and effectors remain poorly characterized. We show here that Wrch-1 distributes along the apical and basolateral membranes in MDCK cells and binds the cell polarity protein P...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00336-08
更新日期:2009-02-01 00:00:00
abstract::In contrast to differentiated somatic cells, mouse embryonal carcinoma (EC) cell lines spontaneously express high levels of major members of the heat shock protein (HSP) family. In addition, some EC cell lines (noninducible) are not able to induce HSP gene transcription and HSP synthesis after a stress. However, after...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.9.3888
更新日期:1989-09-01 00:00:00
abstract::Obesity and type 2 diabetes are characterized by insulin resistance. Mice lacking the protein-tyrosine phosphatase PTP1B in all tissues are hypersensitive to insulin but also have diminished fat stores. Because adiposity affects insulin sensitivity, the extent to which PTP1B directly regulates glucose homeostasis has ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00959-07
更新日期:2007-11-01 00:00:00
abstract::We analyzed the impact of a GAGA element on a transgenic promoter in Drosophila melanogaster that was activated by proteins composed of the Tet(on) DNA binding domain and either the heat shock factor (HSF) activation domain or a potent subdomain of VP16. Permanganate footprinting was used to monitor polymerase II (Pol...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.9.3543-3552.2005
更新日期:2005-05-01 00:00:00
abstract::Mitogen-activated protein (MAP) kinase phosphatase 1 (MKP-1) has been shown to play a critical role in mediating the feedback control of MAP kinase cascades in a variety of cellular processes, including proliferation and stress responsiveness. Although MKP-1 expression is induced by a broad array of extracellular stim...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.23.8213-8224.2001
更新日期:2001-12-01 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::Histone H3 lysine 9 (H3-K9) methylation has been shown to correlate with transcriptional repression and serve as a specific binding site for heterochromatin protein 1 (HP1). In this study, we investigated the relationship between H3-K9 methylation, transcriptional repression, and HP1 recruitment by comparing the effec...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.7.2525-2538.2005
更新日期:2005-04-01 00:00:00
abstract::The establishment of epigenetic marks, such as methylation on histone tails, is mechanistically linked to RNA polymerase II within active genes. To explore the interplay between these modifications in transcribed noncoding as well as coding sequences, we analyzed epigenetic modification and chromatin structure at high...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01684-06
更新日期:2007-02-01 00:00:00
abstract::The FLP protein of the Saccharomyces cerevisiae plasmid 2 microns circle catalyzes site-specific recombination between two repeated segments present on the plasmid. In this paper we present results of experiments we performed to define more precisely the features of the FLP recognition target site, which we propose to...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.10.3357
更新日期:1986-10-01 00:00:00
abstract::The androgen receptor (AR) is a nuclear hormone receptor superfamily member that conveys both trans repression and ligand-dependent trans-activation function. Activation of the AR by dihydrotestosterone (DHT) regulates diverse physiological functions including secondary sexual differentiation in the male and the induc...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.10.3373-3388.2002
更新日期:2002-05-01 00:00:00
abstract::MicroRNA 155 (miR-155) is an oncomir, generated as a noncoding RNA from the BIC gene whose promoter activity is mainly controlled via activation protein 1 (AP-1) and NF-κB transcription factors. We found that the expression levels of miR-155 and programmed cell death 4 (Pdcd4) exhibit inverse relationships in tongue c...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00410-18
更新日期:2019-03-01 00:00:00
abstract::The silent mating-type loci of Saccharomyces cerevisiae, HML and HMR, are flanked by transcriptional silencers that have ARS activity (i.e., they function as replication origins when in plasmids). To test whether these ARS elements are chromosomal origins, we mapped origins near HML (close to the left telomere of chro...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.10.5346
更新日期:1991-10-01 00:00:00
abstract::When herpes simplex virus infects permissive cells, the viral regulatory protein VP16 forms a specific complex with HCF-1, a preexisting nuclear protein involved in cell proliferation. The majority of HCF-1 in the cell is a complex of associated amino (HCF-1(N))- and carboxy (HCF-1(C))-terminal subunits that result fr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.18.6721-6730.2000
更新日期:2000-09-01 00:00:00
abstract::We have analyzed the structures and locations of small nuclear RNA (snRNA) precursors at various stages in their synthesis and maturation. In the nuclei of pulse-labeled Xenopus laevis oocytes, we detected snRNAs that were longer than their mature forms at their 3' ends by up to 10 nucleotides. Analysis of the 5' caps...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.7.3365
更新日期:1990-07-01 00:00:00
abstract::Heat shock proteins (HSPs) are highly conserved among all organisms from prokaryotes to eukaryotes. In mice, the HSP genes Hsp70.1 and Hsp70.3 are induced by both endogenous and exogenous stressors, such as heat and toxicants. In order to determine whether such proteins specifically influence genomic instability, mice...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.2.899-911.2004
更新日期:2004-01-01 00:00:00
abstract::Myocyte enhancer factor 2 (MEF2) transcription factors cooperate with the MyoD family of basic helix-loop-helix (bHLH) transcription factors to drive skeletal muscle development during embryogenesis, but little is known about the potential functions of MEF2 factors in postnatal skeletal muscle. Here we show that skele...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01187-07
更新日期:2007-12-01 00:00:00
abstract::Intracisternal A-particle (IAP) sequences are endogenous retrovirus-like mobile elements, or retrotransposons, present at 1,000 copies in the mouse genome. These elements transpose in a replicative manner via an RNA intermediate and its reverse transcription, and their transposition should therefore be tightly control...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.8.4495
更新日期:1996-08-01 00:00:00
abstract::Meltrin alpha (ADAM12) is a metalloprotease-disintegrin whose specific expression patterns during development suggest that it is involved in myogenesis and the development of other organs. To determine the roles Meltrin alpha plays in vivo, we generated Meltrin alpha-deficient mice by gene targeting. Although the numb...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.1.55-61.2003
更新日期:2003-01-01 00:00:00
abstract::Schizosaccharomyces pombe Cdc5p and its Saccharomyces cerevisiae ortholog, Cef1p, are essential Myb-related proteins implicated in pre-mRNA splicing and contained within large multiprotein complexes. Here we describe the tandem affinity purification (TAP) of Cdc5p- and Cef1p-associated complexes. Using transmission el...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.7.2011-2024.2002
更新日期:2002-04-01 00:00:00
abstract::We recently identified Vav, the product of the vav proto-oncogene, as a guanine nucleotide exchange factor (GEF) for Ras. Vav is enzymatically activated by lymphocyte antigen receptor-coupled protein tyrosine kinases or independently by diglycerides. To further evaluate the physiological role of Vav, we assessed its G...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.2.906
更新日期:1994-02-01 00:00:00
abstract::The GCN4 gene encodes a positive effector of amino acid biosynthetic genes in Saccharomyces cerevisiae. Genetic analysis has suggested that GCN4 is regulated by a hierarchy of interacting positive and negative effectors in response to amino acid starvation. Results presented here for a GCN4-lacZ gene fusion support th...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.9.2349
更新日期:1985-09-01 00:00:00
abstract::Transcription from the Moloney murine leukemia virus (Mo-MuLV) long terminal repeat (LTR) is inhibited in murine stem cells and induced during maturation of these cells. We have investigated whether alterations in the activity of this viral regulatory element also occur during differentiation of human myeloid leukemia...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.8.3571
更新日期:1989-08-01 00:00:00
abstract::DNA in the polyploid macronucleus of the ciliated protozoan Tetrahymena thermophila contains the modified base N6-methyladenine. We identified two GATC sites which are methylated in most or all of the 45 copies of the macronuclear genome. One site is 2 kilobases 5' to the histone H4-I gene, and the other is 5 kilobase...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.7.2364
更新日期:1986-07-01 00:00:00