scholarly journals Differential Cell-Specific Modulation of HOXA10 by Estrogen and Specificity Protein 1 Response Elements

2007 ◽  
Vol 92 (5) ◽  
pp. 1920-1926 ◽  
Author(s):  
Ryan Martin ◽  
Melissa B. Taylor ◽  
Graciela Krikun ◽  
Charles Lockwood ◽  
G. Edda Akbas ◽  
...  
Keyword(s):  
Electrophoretic Mobility ◽  
Tissue Specificity ◽  
Academic Medical Center ◽  
Cell Type ◽  
Mobility Shift ◽  
Response Elements ◽  
Specificity Protein 1 ◽  
Cellular Expression ◽  
Cell Type Specific ◽  
Specificity Protein

Abstract Context: HOX genes are highly evolutionarily conserved regulators of embryonic development. HOXA10 also regulates differentiation of the adult reproductive tract and mammary gland in response to sex steroids. Objective: We recently identified two HOXA10 estrogen response elements (EREs). Here we demonstrate that estrogen-responsive HOXA10 expression is cell type specific. Design and Setting: We conducted an in vitro study at an academic medical center. Main Outcome Measure: Reporter assay, gel shift assays (electrophoretic mobility shift assay), and immunohistochemistry were done. Results: The HOXA10 EREs and a specificity protein 1 (Sp1) binding site differentially drive the cell-type-specific E2 response. In electrophoretic mobility shift assays, both estrogen receptor-α and -β bound both EREs but not the Sp1 site. In reporter assays, both EREs and the Sp1 site demonstrated estrogen responsiveness and tissue specificity; transiently transfected uterine Ishikawa cells or breast MCF-7 cells showed differential responses to E2 treatment. Each response element (Sp1, ERE1, and ERE2) drove distinct differential expression in each cell type. Sp1 protein was expressed in a menstrual-cycle stage-specific expression pattern in endometrium, first expressed in perivascular cells. Conclusions: Tissue specificity inherent to a regulatory element as well as differential cellular expression of transcription factors imparts differential tissue-specific estrogen responsiveness.

scholarly journals Cell Type-Specific Replication of Simian Virus 40 Conferred by Hormone Response Elements in the Late Promoter

2002 ◽  
Vol 76 (13) ◽  
pp. 6762-6770 ◽  
Author(s):  
Michael L. Farrell ◽  
Janet E. Mertz
Keyword(s):  
Simian Virus 40 ◽  
Simian Virus ◽  
Genome Replication ◽  
Hormone Response ◽  
Cell Type ◽  
Late Promoter ◽  
African Green Monkey Kidney ◽  
Response Elements ◽  
Hormone Response Elements ◽  
Cell Type Specific

ABSTRACT The late genes of SV40 are not expressed at significant levels until after the onset of viral DNA replication. We previously identified two hormone response elements (HREs) in the late promoter that contribute to this delay. Mutants defective in these HREs overexpress late RNA at early, but not late, times after transfection of CV-1PD cells. Overexpression of nuclear receptors (NRs) that recognize these HREs leads to repression of the late promoter in a sequence-specific and titratable manner, resulting in a delay in late gene expression. These observations led to a model in which the late promoter is repressed at early times after infection by NRs, with this repression being relieved by titration of these repressors through simian virus 40 (SV40) genome replication to high copy number. Here, we tested this model in the context of the viral life cycle. SV40 genomes containing mutations in either or both HREs that significantly reduce NR binding without altering the coding of any proteins were constructed. Competition for replication between mutant and wild-type viruses in low-multiplicity coinfections indicated that the +1 HRE offered a significant selective advantage to the virus within a few cycles of infection in African green monkey kidney cell lines CV-1, CV-1P, TC-7, MA-134, and Vero but not in CV-1PD′ cells. Interestingly, the +55 HRE offered a selective disadvantage in MA-134 cells but had no effect in CV-1, CV-1P, TC-7, Vero, and CV-1PD′ cells. Thus, we conclude that these HREs are biologically important to the virus, but in a cell type-specific manner.

Identification of a cell-type-specific transcriptional repressor in the promoter region of the mouse hepatocyte growth factor gene

1994 ◽  
Vol 14 (11) ◽  
pp. 7046-7058
Author(s):  
Y Liu ◽  
A B Beedle ◽  
L Lin ◽  
A W Bell ◽  
R Zarnegar
Keyword(s):  
Epithelial Cells ◽  
Promoter Region ◽  
Nuclear Protein ◽  
Transcriptional Repressor ◽  
Cell Type ◽  
Mobility Shift ◽  
A Cell ◽  
Cell Type Specific ◽  
Gel Mobility Shift ◽  
Hepatocyte Growth

Hepatocyte growth factor (HGF), a cytokine with multiple functions, exhibits cell-type-specific as well as cytokine- and steroid hormone-regulated expression. The HGF gene is known to be expressed predominately in mesenchymal but not in epithelial cells. In this study, we report the identification of a cell-type-specific transcriptional repressor in the promoter region of the mouse HGF gene, which is evidently responsible for the suppression of HGF expression in epithelial cells. Gel mobility shift assays and DNase I footprinting studies revealed that a 27-bp element (-16 to +11) around the transcription initiation site is responsible for the binding of a nuclear protein which is present in epithelial but not in mesenchymally derived cells. Further analysis of the binding activity of the DNA region with nuclear protein revealed that an approximately 19-bp sequence containing a unique palindromic structure (5'-AACCGACCGGTT-3') overlapped by a CAP box is essential for binding. Substitution of a single base (the contact site) within this region by site-directed mutagenesis resulted in total abrogation of the binding of the nuclear protein and a concomitant increase in the transcriptional activity of various lengths of HGF-chloramphenicol acetyltransferase fused genes when transfected into the epithelial cell line RL95-2 but not the mesenchymal cell line NIH 3T3. Southwestern (DNA-protein) analyses revealed that the nuclear protein which binds to this repressor element is a single polypeptide of approximately 70 kDa. Analysis of the nuclear extract prepared from regenerating mouse liver at various times after two-thirds partial hepatectomy by gel mobility shift assay revealed a substantial reduction (more than 75% within 3 h) in the binding of the repressor to its cognate binding site. Our results suggest that a cis-acting transcriptional repressor in the promoter region of the mouse HGF gene is involved in cell-type-specific regulation through binding to its cognate trans-acting protein which exists in epithelial cells but is absent in fibroblast cells.

scholarly journals Identification of a cell-type-specific transcriptional repressor in the promoter region of the mouse hepatocyte growth factor gene.

1994 ◽  
Vol 14 (11) ◽  
pp. 7046-7058 ◽  
Author(s):  
Y Liu ◽  
A B Beedle ◽  
L Lin ◽  
A W Bell ◽  
R Zarnegar
Keyword(s):  
Epithelial Cells ◽  
Promoter Region ◽  
Nuclear Protein ◽  
Transcriptional Repressor ◽  
Cell Type ◽  
Mobility Shift ◽  
A Cell ◽  
Cell Type Specific ◽  
Gel Mobility Shift ◽  
Hepatocyte Growth

Hepatocyte growth factor (HGF), a cytokine with multiple functions, exhibits cell-type-specific as well as cytokine- and steroid hormone-regulated expression. The HGF gene is known to be expressed predominately in mesenchymal but not in epithelial cells. In this study, we report the identification of a cell-type-specific transcriptional repressor in the promoter region of the mouse HGF gene, which is evidently responsible for the suppression of HGF expression in epithelial cells. Gel mobility shift assays and DNase I footprinting studies revealed that a 27-bp element (-16 to +11) around the transcription initiation site is responsible for the binding of a nuclear protein which is present in epithelial but not in mesenchymally derived cells. Further analysis of the binding activity of the DNA region with nuclear protein revealed that an approximately 19-bp sequence containing a unique palindromic structure (5'-AACCGACCGGTT-3') overlapped by a CAP box is essential for binding. Substitution of a single base (the contact site) within this region by site-directed mutagenesis resulted in total abrogation of the binding of the nuclear protein and a concomitant increase in the transcriptional activity of various lengths of HGF-chloramphenicol acetyltransferase fused genes when transfected into the epithelial cell line RL95-2 but not the mesenchymal cell line NIH 3T3. Southwestern (DNA-protein) analyses revealed that the nuclear protein which binds to this repressor element is a single polypeptide of approximately 70 kDa. Analysis of the nuclear extract prepared from regenerating mouse liver at various times after two-thirds partial hepatectomy by gel mobility shift assay revealed a substantial reduction (more than 75% within 3 h) in the binding of the repressor to its cognate binding site. Our results suggest that a cis-acting transcriptional repressor in the promoter region of the mouse HGF gene is involved in cell-type-specific regulation through binding to its cognate trans-acting protein which exists in epithelial cells but is absent in fibroblast cells.

scholarly journals Characterization of adherens junction protein expression and localization in pituitary cell networks

2009 ◽  
Vol 202 (3) ◽  
pp. 375-387 ◽  
Author(s):  
Norbert Chauvet ◽  
Taoufik El-Yandouzi ◽  
Marie-Noëlle Mathieu ◽  
Audrey Schlernitzauer ◽  
Evelyne Galibert ◽  
...  
Keyword(s):  
Anterior Pituitary ◽  
Functional Organization ◽  
Pituitary Cell ◽  
Cell Contact ◽  
Cell Type ◽  
Cellular Expression ◽  
Junction Protein ◽  
Cell Type Specific ◽  
Cell Networks ◽  
Cell Cell

Our view of anterior pituitary organization has been altered with the recognition that folliculo-stellate (FS) and somatotroph cell populations form large-scale three-dimensional homotypic networks. This morphological cellular organization may optimize communication within the pituitary gland promoting coordinated pulsatile secretion adapted to physiological needs. The aim of this study was to identify the molecules involved in the formation and potential functional organization and/or signaling within these cell–cell networks. Here, we have focused on one class of cell adhesion molecules, the cadherins, since β-catenin has been detected in the GH cell network. We have characterized, by qPCR and immunohistochemistry, their cellular expression and distribution. We have also examined whether their expression could be modulated during pituitary tissue remodeling. The mouse anterior pituitary has a restricted and cell-type specific repertoire of cadherin expression: cadherin-11 is exclusively expressed in TSH cells; N-cadherin displays a ubiquitous expression pattern but with different levels of expression between endocrine cell types; E-cadherin is restricted to homotypic contacts between FS cells; while cadherin-18 is expressed both in somatotrophs and FS cells. Thus, each cell type presents a defined combinatorial expression of different subsets of cadherins. This cell-type specific cadherin expression profile emerges early during development and undergoes major changes during postnatal development. These results suggest the existence within the anterior pituitary of cell–cell contact signaling based on a defined pattern of cadherin expression, which may play a crucial role in cellular recognition during the formation and fate of pituitary cell homotypic networks.

scholarly journals Localization of a repressive sequence contributing to B-cell specificity in the immunoglobulin heavy-chain enhancer.

1988 ◽  
Vol 8 (2) ◽  
pp. 988-992 ◽  
Author(s):  
J Weinberger ◽  
P S Jat ◽  
P A Sharp
Keyword(s):  
Heavy Chain ◽  
Tissue Specificity ◽  
Immunoglobulin Heavy Chain ◽  
Cell Type ◽  
Cis Acting ◽  
Lymphoid Lineage ◽  
Cell Specificity ◽  
Cell Type Specific ◽  
Minimal Sequences ◽  
Repressor Element

The immunoglobulin heavy-chain enhancer is a cis-acting element which activates transcription of nearby genes only in cells of the lymphoid lineage. To identify the minimal sequences necessary to impart cell type transcriptional specificity, we tested the activity of several deletions and internal mutations in the mu enhancer. Experiments involving measurement of both chloramphenicol acetyltransferase activity and RNA levels indicated the presence of a dominant repressor element within the mu enhancer. This repressive activity was detected in fibroblasts but not in myeloma cells. Removal or disruption of this repressor element revealed the presence of elements within the mu enhancer that activate transcription in fibroblasts. Thus, enhancer tissue specificity is in part due to the composite of both constitutive activation and cell-type-specific repressive activity. The possible biological roles of this phenomenon are discussed.

scholarly journals Flux analysis of cholesterol biosynthesis in vivo reveals multiple tissue and cell-type specific pathways

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Matthew A Mitsche ◽  
Jeffrey G McDonald ◽  
Helen H Hobbs ◽  
Jonathan C Cohen
Keyword(s):  
Tissue Specificity ◽  
Isotope Labeling ◽  
Cultured Cells ◽  
Cholesterol Biosynthesis ◽  
Flux Analysis ◽  
Preputial Gland ◽  
Cell Type ◽  
Isotopomer Analysis ◽  
Cell Type Specific

Two parallel pathways produce cholesterol: the Bloch and Kandutsch-Russell pathways. Here we used stable isotope labeling and isotopomer analysis to trace sterol flux through the two pathways in mice. Surprisingly, no tissue used the canonical K–R pathway. Rather, a hybrid pathway was identified that we call the modified K–R (MK–R) pathway. Proportional flux through the Bloch pathway varied from 8% in preputial gland to 97% in testes, and the tissue-specificity observed in vivo was retained in cultured cells. The distribution of sterol isotopomers in plasma mirrored that of liver. Sterol depletion in cultured cells increased flux through the Bloch pathway, whereas overexpression of 24-dehydrocholesterol reductase (DHCR24) enhanced usage of the MK–R pathway. Thus, relative use of the Bloch and MK–R pathways is highly variable, tissue-specific, flux dependent, and epigenetically fixed. Maintenance of two interdigitated pathways permits production of diverse bioactive sterols that can be regulated independently of cholesterol.

scholarly journals Whole-body integration of gene expression and single-cell morphology

2020 ◽  
Author(s):  
Hernando M. Vergara ◽  
Constantin Pape ◽  
Kimberly I. Meechan ◽  
Valentyna Zinchenko ◽  
Christel Genoud ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
High Resolution Electron Microscopy ◽  
Cell Types ◽  
Whole Body ◽  
Specific Gene ◽  
Entire Body ◽  
Cell Type ◽  
Cellular Expression ◽  
Cell Type Specific

SummaryAnimal bodies are composed of hundreds of cell types that differ in location, morphology, cytoarchitecture, and physiology. This is reflected by cell type-specific transcription factors and downstream effector genes implementing functional specialisation. Here, we establish and explore the link between cell type-specific gene expression and subcellular morphology for the entire body of the marine annelid Platynereis dumerilii. For this, we registered a whole-body cellular expression atlas to a high-resolution electron microscopy dataset, automatically segmented all cell somata and nuclei, and clustered the cells according to gene expression or morphological parameters. We show that collective gene expression most efficiently identifies spatially coherent groups of cells that match anatomical boundaries, which indicates that combinations of regionally expressed transcription factors specify tissue identity. We provide an integrated browser as a Fiji plugin to readily explore, analyse and visualise multimodal datasets with remote on-demand access to all available datasets.

scholarly journals MHC I–associated peptides preferentially derive from transcripts bearing miRNA response elements

Blood ◽  
2012 ◽  
Vol 119 (26) ◽  
pp. e181-e191 ◽  
Author(s):  
Diana Paola Granados ◽  
Wafaa Yahyaoui ◽  
Céline M. Laumont ◽  
Tariq Daouda ◽  
Tara L. Muratore-Schroeder ◽  
...  
Keyword(s):  
Cell Surface ◽  
B Lymphocytes ◽  
Essential Role ◽  
Physical Nature ◽  
Cell Type ◽  
Mhc I ◽  
Response Elements ◽  
Human B Cells ◽  
A Cell ◽  
Cell Type Specific

Abstract MHC I–associated peptides (MIPs) play an essential role in normal homeostasis and diverse pathologic conditions. MIPs derive mainly from defective ribosomal products (DRiPs), a subset of nascent proteins that fail to achieve a proper conformation and the physical nature of which remains elusive. In the present study, we used high-throughput proteomic and transcriptomic methods to unravel the structure and biogenesis of MIPs presented by HLA-A and HLA-B molecules on human EBV-infected B lymphocytes from 4 patients. We found that although HLA-different subjects present distinctive MIPs derived from different proteins, these MIPs originate from proteins that are functionally interconnected and implicated in similar biologic pathways. Secondly, the MIP repertoire of human B cells showed no bias toward conserved versus polymorphic genomic sequences, were derived preferentially from abundant transcripts, and conveyed to the cell surface a cell-type–specific signature. Finally, we discovered that MIPs derive preferentially from transcripts bearing miRNA response elements. Furthermore, whereas MIPs of HLA-disparate subjects are coded by different sets of transcripts, these transcripts are regulated by mostly similar miRNAs. Our data support an emerging model in which the generation of MIPs by a transcript depends on its abundance and DRiP rate, which is regulated to a large extent by miRNAs.

scholarly journals Epithelial tumor suppressor ELF3 is a lineage-specific amplified oncogene in lung adenocarcinoma

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Katey S. S. Enfield ◽  
Erin A. Marshall ◽  
Christine Anderson ◽  
Kevin W. Ng ◽  
Sara Rahmati ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Prognostic Value ◽  
Tissue Specificity ◽  
Clinical Evidence ◽  
Gene Dosage ◽  
Cell Type ◽  
Epithelial Tumor ◽  
Subtype Specificity ◽  
Cell Type Specific ◽  
Pan Cancer

AbstractGene function in cancer is often cell type-specific. The epithelial cell-specific transcription factor ELF3 is a documented tumor suppressor in many epithelial tumors yet displays oncogenic properties in others. Here, we show that ELF3 is an oncogene in the adenocarcinoma subtype of lung cancer (LUAD), providing genetic, functional, and clinical evidence of subtype specificity. We discover a region of focal amplification at chromosome 1q32.1 encompassing the ELF3 locus in LUAD which is absent in the squamous subtype. Gene dosage and promoter hypomethylation affect the locus in up to 80% of LUAD analyzed. ELF3 expression was required for tumor growth and a pan-cancer expression network analysis supports its subtype and tissue specificity. We further show that ELF3 displays strong prognostic value in LUAD but not LUSC. We conclude that, contrary to many other tumors of epithelial origin, ELF3 is an oncogene and putative therapeutic target in LUAD.

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