Abstract:
:Endothelial cells differentiate from mesoderm-derived precursors to initiate the earliest events in vascular development. Although the signaling events that regulate the successive steps of vascular development are known in some detail, the transcriptional processes that regulate the first steps in vasculogenesis are not well defined. We have studied the regulatory mechanisms of flk1 expression as a model to understand the upstream events in endothelial cell differentiation, since flk1 is the earliest marker of endothelial precursors. Using a variety of biochemical approaches, we identified a cis-acting element in the first intron of the flk1 gene that is required for endothelium-dependent expression in transgenic reporter gene assays. Using the yeast one-hybrid system, we identified HoxB5 as the transcription factor that binds this cis-acting element, the HoxB5-binding element (HBE). HoxB5 mRNA colocalized with flk1 expression in differentiating embryoid bodies, and HoxB5 potently transactivated the flk1 promoter in an HBE-dependent fashion in transient-transfection assays. Overexpression of HoxB5 led to expansion of flk1(+) angioblasts in differentiating embryoid bodies and increased the number of PECAM (platelet-endothelial cell adhesion molecule)-positive primitive blood vessels. HoxB5 is necessary and sufficient to activate the cell-intrinsic events that regulate the differentiation of angioblasts and mature endothelial cells from their mesoderm-derived precursors.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Wu Y,Moser M,Bautch VL,Patterson Cdoi
10.1128/mcb.23.16.5680-5691.2003subject
Has Abstractpub_date
2003-08-01 00:00:00pages
5680-91issue
16eissn
0270-7306issn
1098-5549journal_volume
23pub_type
杂志文章abstract::We investigated the role of RNA polymerase II (pol II) carboxy-terminal domain (CTD) phosphorylation in pre-mRNA processing coupled and uncoupled from transcription in Xenopus oocytes. Inhibition of CTD phosphorylation by the kinase inhibitors 5,6-dichloro-1beta-D-ribofuranosyl-benzimidazole and H8 blocked transcripti...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.20.8963-8969.2004
更新日期:2004-10-01 00:00:00
abstract::GATA1 is a master regulator of erythropoiesis, expression of which is regulated by multiple discrete cis-acting elements. In this study, we examine the activity of a promoter-proximal double GATA (dbGATA) motif, using a Gata1 bacterial artificial chromosome (BAC)-transgenic green fluorescent protein (GFP) reporter (G1...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01011-14
更新日期:2015-03-01 00:00:00
abstract::Phosphorylation is one of the key mechanisms that regulate centrosome biogenesis, spindle assembly, and cell cycle progression. However, little is known about centrosome-specific phosphorylation sites and their functional relevance. Here, we identified phosphoproteins of intact Drosophila melanogaster centrosomes and ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00814-12
更新日期:2012-09-01 00:00:00
abstract::The retinoblastoma tumor suppressor protein (RB) is a negative regulator of the cell cycle that inhibits both G(1) and S-phase progression. While RB-mediated G(1) inhibition has been extensively studied, the mechanism utilized for S-phase inhibition is unknown. To delineate the mechanism through which RB inhibits DNA ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.12.4032-4045.2001
更新日期:2001-06-01 00:00:00
abstract::rRNA transcription in Xenopus laevis terminates near a 7-base-pair (bp) conserved sequence (T3 box) located 200 bp upstream of the site of transcription initiation for the adjacent gene promoter. We present evidence here that a 12-bp element containing the T3 box is an essential part of the terminator. Using an oocyte...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.5.1900
更新日期:1987-05-01 00:00:00
abstract::Interleukin-5 (IL-5) and IL-6 have both been reported to act as B-cell differentiation factors by stimulating activated B cells to secrete antibody. However, it has not been possible to directly compare the effects of these two lymphokines because of the lack of a suitable B-cell line capable of responding to both. We...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.7.3929
更新日期:1993-07-01 00:00:00
abstract::Insulin gene transcription relies on enhancer and promoter elements which are active in pancreatic beta cells. We showed that adenovirus type 5 infection of HIT T-15 cells, a transformed hamster beta cell line, represses insulin gene transcription and mRNA levels. Using expression plasmids transiently introduced into ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.3.1164
更新日期:1987-03-01 00:00:00
abstract::Pretreatment of 3T6 murine cells with the carcinogen UV radiation or N-acetoxy-N-acetylaminofluorene increased the number of methotrexate-resistant colonies. This carcinogen-induced enhancement was seen only at low toxicities. The enhancement was transient and was observed at its maximum when cells were subjected to m...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.6.1050
更新日期:1984-06-01 00:00:00
abstract::Rapid kinetic techniques were employed to measure the transport of adenine in adenine phosphoribosyltransferase-deficient L929 and Chinese hamster ovary (CHO) cells in zero-trans entry and exit and equilibrium exchange procedures. The kinetic parameters of transport were computed by fitting appropriate integrated rate...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.3.1.82
更新日期:1983-01-01 00:00:00
abstract::Net, Elk-1, and Sap-1 are members of the ternary complex factor (TCF) subfamily of Ets transcription factors. They form ternary complexes with serum response factor (SRF) on serum response elements of immediate early genes such as c-fos and egr-1 and mediate responses to growth factors and mitogen-activated protein ki...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.24.10853-10862.2005
更新日期:2005-12-01 00:00:00
abstract::The muscle LIM protein (MLP) and cofilin 2 (CFL2) are important regulators of striated myocyte function. Mutations in the corresponding genes have been directly associated with severe human cardiac and skeletal myopathies, and aberrant expression patterns have often been observed in affected muscles. Herein, we have i...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00654-09
更新日期:2009-11-01 00:00:00
abstract::Neighboring genes encoding the mouse sex-limited protein (Slp) and fourth component of complement (C4) show extensive homology. In contrast to C4, however, Slp is regulated by androgen. One region of the Slp gene capable of hormonal response following transfection was located about 2 kilobases upstream of the transcri...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.6.2350
更新日期:1988-06-01 00:00:00
abstract::The molecular distinctions between mortality stages 1 (M1; senescence) and 2 (M2; crisis) of human replicative aging are ill defined. We demonstrate a qualitative difference between telomeric end associations at M1 and the end fusions that produce dicentric chromosomes and breakage-fusion cycles. Knockdown of ligase I...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01569-08
更新日期:2009-05-01 00:00:00
abstract::The GTPase-activating protein (GAP) stimulates the GTPase reaction of p21 by 5 orders of magnitude such that the kcat of the reaction is increased to 19 s-1. Mutations of residues in loop L1 (Gly-12 and Gly-13), in loop L2 (Thr-35 and Asp-38), and in loop L4 (Gln-61 and Glu-63) influence the reaction in different ways...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.5.2050
更新日期:1992-05-01 00:00:00
abstract::The simian virus 40 72-base-pair repeats substituted for the polyomavirus enhancer, allowing replication and transcription in mouse 3T6 but not monkey CV-1 cells. A polyomavirus genome containing the entire simian virus 40 control region replicated at low levels in 3T6 and CV-1 cells; however, transcripts were detecte...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.6.1534
更新日期:1985-06-01 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::Simultaneous resistance to an array of drugs with different cytotoxic activities is a property of Saccharomyces cerevisiae, in which the protein Pdr3p has recently been shown to play a role as a transcriptional regulator. We provide evidence that the yeast PDR3 gene, which encodes a zinc finger transcription factor im...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.8.4043
更新日期:1995-08-01 00:00:00
abstract::Loss of heterozygosity (LOH) is a common genetic alteration in tumors and often extends several megabases to encompass multiple genetic loci or even whole chromosome arms. Based on marker and karyotype analysis of tumor samples, a significant fraction of LOH events appears to arise from mitotic recombination between h...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.2.733-743.2003
更新日期:2003-01-01 00:00:00
abstract::The xCR1 protein is a maternal determinant and cofactor for nodal signaling in vertebrate embryos. The xCR1 protein accumulates specifically in the animal cells of Xenopus embryos, but maternal xCR1 mRNA is distributed equally throughout all embryonic cells. Here, we show that vegetal cell-specific translational repre...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01865-08
更新日期:2009-07-01 00:00:00
abstract::The human genome contains a number of methyl CpG binding proteins that translate DNA methylation into a physiological response. To gain insight into the function of MBD2 and MBD3, we first applied protein tagging and mass spectrometry. We show that MBD2 and MBD3 assemble into mutually exclusive distinct Mi-2/NuRD-like...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.3.843-851.2006
更新日期:2006-02-01 00:00:00
abstract::Protein phosphatase 2A (PP2A) is a multimeric serine/threonine phosphatase that carries out multiple functions. Although numerous observations suggest that PP2A plays a major role in downregulation of the mitogen-activated protein (MAP) kinase pathway, the precise mechanisms are unknown. To clarify the role of PP2A in...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.7.2375-2387.2002
更新日期:2002-04-01 00:00:00
abstract::Resistance to the growth-inhibitory action of retinoic acid (RA), the bioactive derivative of vitamin A, is common in human tumors. One form of RA resistance has been associated with silencing and hypermethylation of the retinoic acid receptor beta2 gene (RARbeta2), an RA-regulated tumor suppressor gene. The presence ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.23.10591-10603.2005
更新日期:2005-12-01 00:00:00
abstract::Rap1 (repressor activator protein 1) is a conserved multifunctional protein initially identified as a transcriptional regulator of ribosomal protein genes in Saccharomyces cerevisiae but subsequently shown to play diverse functions at multiple chromosomal loci, including telomeres. The function of Rap1 appears to be e...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00986-09
更新日期:2010-03-01 00:00:00
abstract::The Polycomb group proteins are transcriptional repressors that are thought to act through multimeric nuclear complexes. We show that ph and Psc coprecipitate with Pc from nuclear extracts. We have analyzed the domains required for the association of Psc with ph and Pc by using the yeast two-hybrid system and an in vi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.5.2712
更新日期:1998-05-01 00:00:00
abstract::Inactivating mutations within the von Hippel-Lindau (VHL) tumor suppressor gene predispose patients to develop a variety of highly vascularized tumors. pVHL targets alpha subunits of the heterodimeric transcription factor hypoxia-inducible factor (HIF), a critical regulator of energy metabolism, angiogenesis, hematopo...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.11.4565-4578.2005
更新日期:2005-06-01 00:00:00
abstract::Inorganic pyrophosphate promoted the acidification of an intracellular compartment in permeabilized procyclic trypomastigotes of Trypanosoma brucei, as measured by acridine orange uptake. The proton gradient generated by pyrophosphate was collapsed by addition of nigericin or NH(4)Cl. Pyrophosphate-driven proton trans...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.11.7712
更新日期:1999-11-01 00:00:00
abstract::The 3' noncoding region element (AUUUA)n specifically targets many short-lived mRNAs for degradation. Although the mechanism by which this sequence functions is not yet understood, a potential link between facilitated mRNA turnover and translation has been implied by the stabilization of cellular mRNAs in the presence...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.3.1971
更新日期:1993-03-01 00:00:00
abstract::beta-Site beta-amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is the beta-secretase in vivo for processing APP to generate amyloid beta protein (Abeta). Abeta deposition in the brain is the hallmark of Alzheimer's disease (AD) neuropathology. Inhibition of BACE1 activity has major pharmaceutical potential f...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.9.3353-3364.2006
更新日期:2006-05-01 00:00:00
abstract::A molecular karyotype of Neurospora crassa was obtained by using an alternating-field gel electrophoresis system which employs contour-clamped homogeneous electric fields. The migration of all seven N. crassa chromosomal DNAs was defined, and five of the seven molecules were separated from one another. The estimated s...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.4.1469
更新日期:1988-04-01 00:00:00
abstract::Erythroid Krüppel-like factor (EKLF [KLF1]) is a transcriptional regulator that plays a critical role within a specific subset of hematopoietic cells, particularly in the erythroid lineage and its immediate precursor, the megakaryocyte-erythroid progenitor (MEP). We find that EKLF is posttranslationally modified by su...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00589-07
更新日期:2007-12-01 00:00:00