scholarly journals T cell receptor beta gene has two downstream DNase I hypersensitive regions. Possible mechanisms of tissue- and stage-specific gene regulation.

1989 ◽  
Vol 169 (6) ◽  
pp. 2097-2107 ◽  
Author(s):  
Y Hashimoto
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Cell Lines ◽  
Regulatory Elements ◽  
Dnase I ◽  
The Other ◽  
Specific Gene ◽  
Enhancer Element ◽  
Tissue Specific ◽  
T Cell Lines

Two DNase I-hypersensitive regions were identified downstream of the TCR gene constant region. One of these regions is located at the site of a putative enhancer element and was observed only in T cell lines and not in cell lines derived from other tissues. The other DNase-hypersensitive region was also detected only in T cell lines but only in those expressing TCR-beta RNA. Thus, the first region is probably tissue specific, while the second region is probably tissue and stage specific. The DNA sequence of the second DNase I-hypersensitive region revealed several stretches of nucleotides that are characteristic of consensus sequences for regulatory elements. These results, together with the observations in transgenic mice that indicate a requirement for two distinct regions for optimal TCR gene expression, suggest the presence of at least two regulatory regions downstream of the C-beta-2 region; one is an enhancer region and the other is a transcriptionally related regulatory region. The tissue/stage specificity of these DNase I-hypersensitive regions supports the notion that changes in chromatin structure control tissue-specific gene expression.

scholarly journals Type B Leukemogenic Virus Has a T-Cell-Specific Enhancer That Binds AML-1

2001 ◽  
Vol 75 (5) ◽  
pp. 2174-2184 ◽  
Author(s):  
Jennifer A. Mertz ◽  
Farah Mustafa ◽  
Shari Meyers ◽  
Jaquelin P. Dudley
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Protein Complexes ◽  
Regulatory Elements ◽  
Single Mutation ◽  
Type B ◽  
Enhancer Activity ◽  
Enhancer Element ◽  
Enhancer Function ◽  
T Cell Lines

ABSTRACT Type B leukemogenic virus (TBLV) induces rapidly appearing T-cell tumors in mice. TBLV is highly related to mouse mammary tumor virus (MMTV) except that TBLV long terminal repeats (LTRs) have a deletion of negative regulatory elements and a triplication of sequences flanking the deletion. To determine if the LTR triplication represents a viral enhancer element, we inserted the triplication upstream and downstream in either orientation relative to the thymidine kinase promoter linked to the luciferase gene. These experiments showed that upregulation of reporter gene activity by the TBLV triplication was relatively orientation independent, consistent with the activity of eukaryotic enhancer elements. TBLV enhancer activity was observed in T-cell lines but not in fibroblasts, B cells, or mammary cells, suggesting that enhancer function is cell type dependent. To analyze the transcription factor binding sites that are important for TBLV enhancer function, we prepared substitution mutations in a reconstituted C3H MMTV LTR that recapitulates the deletion observed in the TBLV LTR. Transient transfections showed that a single mutation (556M) decreased TBLV enhancer activity at least 20-fold in two different T-cell lines. This mutation greatly diminished AML-1 (recently renamed RUNX1) binding in gel shift assays with a mutant oligonucleotide, whereas AML-1 binding to a wild-type TBLV oligomer was specific, as judged by competition and supershift experiments. The 556 mutation also reduced TBLV enhancer binding of two other protein complexes, called NF-A and NF-B, that did not appear to be related to c-Myb or Ets. AML-1overexpression in a mammary cell line enhanced expression from the TBLV LTR approximately 30-fold. These data suggest that binding of AML-1 to the TBLV enhancer, likely in combination with other factors, is necessary for optimal enhancer function.

Epigenetics of Cellular Memory: Insights from the Chromatin Accessibility Landscape of the Mitotic Genome

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4342-4342
Author(s):  
Chris C.S. Hsiung ◽  
Christapher Morrissey ◽  
Maheshi Udugama ◽  
Christopher Frank ◽  
Cheryl A. Keller ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Transcription Factors ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Dnase I ◽  
Specific Gene ◽  
Tissue Specific ◽  
Dnase I Sensitivity ◽  
Mitotic Chromatin

Abstract Normal development requires the coordination of cell cycle progression and gene expression to produce physiologically appropriate cell numbers of various lineages. The concomitant dysregulation of these two cellular programs is central to many malignant and non-malignant hematologic diseases, yet researchers still lack clear, general principles of how intrinsic properties of cell division could influence transcriptional regulation. Mitosis is a unique phase of the cell cycle that dramatically disrupts transcription: chromosomes condense to form microscopically recognizable structures, the nucleus is disassembled, RNA synthesis ceases, and the transcription machinery and many transcription factors are evicted from mitotic chromatin. How cells “remember” tissue-specific transcriptional programs through mitotic divisions remains largely unknown. Some transcription factors, including the erythroid master regulator, GATA1, and certain chromatin features are known to remain associated with DNA during mitosis. These molecular entities have been proposed to serve as mitotic “bookmarks” -- molecules that store gene regulatory information at individual loci through mitosis. However, we have limited knowledge of the composition, mechanism and function of mitotic bookmarks. In this context, chromatin structure deserves special consideration, as chromosome condensation during mitosis could potentially hinder transcription factor binding. To obtain the first genome-wide view of chromatin accessibility during mitosis, we mapped the DNase I sensitivity of the interphase versus mitotic genome in two maturation stages in a murine erythroblast cell line, G1E. Despite microscopic condensation of chromosomes during mitosis, we found that DNase I sensitivity is extensively preserved throughout the mappable genome, indicating that mitotic chromatin is not as condensed as commonly presumed. Individual genes and cis-regulatory elements can maintain all, part of, or none of its interphase accessibility during mitosis, demonstrating that accessibility of mitotic chromatin is locally specified. Promoters generally maintain accessibility during mitosis; moreover, promoters with the highest degree of accessibility preservation in mitosis in G1E cells tend to also be accessible across many murine tissues in interphase. In contrast to promoters, we found that enhancer accessibility is preferentially lost during mitosis, raising the possibility that memory of enhancer regulation may be altered during mitosis. Since enhancers play crucial roles in specifying tissue-specific gene expression patterns, we propose that this phase of the cell cycle may be especially susceptible to resetting of transcriptional programs. This hypothesis is supported by our preliminary results that revealed aberrant RNA polymerase II re-engagement with the genome and transcript production in early G1. Thus, mitosis could be a source of gene expression heterogeneity, with potential implications for cell fate transitions in proliferative cells, such as during stem cell lineage commitment, experimental reprogramming, and tumorigenesis. Disclosures No relevant conflicts of interest to declare.

scholarly journals Distinct DNase-I hypersensitive sites are associated with TAL-1 transcription in erythroid and T-cell lines

Blood ◽  
1994 ◽  
Vol 84 (11) ◽  
pp. 3819-3827 ◽  
Author(s):  
K Leroy-Viard ◽  
MA Vinit ◽  
N Lecointe ◽  
D Mathieu-Mahul ◽  
PH Romeo
Keyword(s):  
T Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Cpg Island ◽  
Regulatory Elements ◽  
Dnase I ◽  
Dnase I Hypersensitive Sites ◽  
Hypersensitive Sites ◽  
T Cell Lines ◽  
Megakaryocytic Cell

The tal-1 gene, frequently activated in human T-cell acute lymphoblastic leukemia (T-ALL), is expressed in the erythroid, megakaryocytic, and mast cell lineages during normal hematopoiesis. To gain further insight into the molecular mechanisms that control tal-1 expression, we investigated tal-1 chromatin structure in erythroid/megakaryocytic cell lines and in T-cell lines either with or without tal-1 rearrangements. Tal-1 transcription was shown to be monoallelic in Jurkat, a T-cell line that expresses tal-1 in the absence of apparent genomic alteration of the locus. Methylation studies indicated that the tal-152 GC-rich region behaves like a CpG island, hypomethylated in normal cells, and methylated de novo on transcriptionally inactive alleles in established cell lines. Five major DNase-I hypersensitive sites (HS) were mapped in the tal-1 locus. HS I, IV, and V were exclusively observed in the erythroid/megakaryocytic cell lines that express tal-1 from the promoters 1a and 1b. HS II was weak in hematopoietic cell lines, absent in Hela, and greatly enhanced in Jurkat, suggesting that this region might be implicated in the cis-activation of tal-1 promoter 1b in this cell line. HS III was weak in HEL and Jurkat, and greatly enhanced in DU528, a T-cell line that bears a t (1;14) and initiates tal-1 transcription within exon 4. These results suggest that distinct regulatory elements are associated with the use of the different tal-1 promoters.

scholarly journals Methylation of the Cyclin A1 Promoter Correlates with Gene Silencing in Somatic Cell Lines, while Tissue-Specific Expression of Cyclin A1 Is Methylation Independent

2000 ◽  
Vol 20 (9) ◽  
pp. 3316-3329 ◽  
Author(s):  
Carsten Müller ◽  
Carol Readhead ◽  
Sven Diederichs ◽  
Gregory Idos ◽  
Rong Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Promoter Methylation ◽  
Cpg Island ◽  
Trichostatin A ◽  
Specific Gene ◽  
Cyclin A1 ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression

ABSTRACT Gene expression in mammalian organisms is regulated at multiple levels, including DNA accessibility for transcription factors and chromatin structure. Methylation of CpG dinucleotides is thought to be involved in imprinting and in the pathogenesis of cancer. However, the relevance of methylation for directing tissue-specific gene expression is highly controversial. The cyclin A1 gene is expressed in very few tissues, with high levels restricted to spermatogenesis and leukemic blasts. Here, we show that methylation of the CpG island of the human cyclin A1 promoter was correlated with nonexpression in cell lines, and the methyl-CpG binding protein MeCP2 suppressed transcription from the methylated cyclin A1 promoter. Repression could be relieved by trichostatin A. Silencing of a cyclin A1 promoter-enhanced green fluorescent protein (EGFP) transgene in stable transfected MG63 osteosarcoma cells was also closely associated with de novo promoter methylation. Cyclin A1 could be strongly induced in nonexpressing cell lines by trichostatin A but not by 5-aza-cytidine. The cyclin A1 promoter-EGFP construct directed tissue-specific expression in male germ cells of transgenic mice. Expression in the testes of these mice was independent of promoter methylation, and even strong promoter methylation did not suppress promoter activity. MeCP2 expression was notably absent in EGFP-expressing cells. Transcription from the transgenic cyclin A1 promoter was repressed in most organs outside the testis, even when the promoter was not methylated. These data show the association of methylation with silencing of the cyclin A1 gene in cancer cell lines. However, appropriate tissue-specific repression of the cyclin A1 promoter occurs independently of CpG methylation.

scholarly journals Unique Gene Expression Patterns in Human T-cell Lines Generated from Multiple Sclerosis Patients by Stimulation with a Synthetic MOG Peptide

2005 ◽  
Vol 12 (3) ◽  
pp. 203-209 ◽  
Author(s):  
Mathilda Mandel ◽  
Michael Gurevich ◽  
Gad Lavie ◽  
Irun R. Cohen ◽  
Anat Achiron
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
Healthy Subjects ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Gene Expression Patterns ◽  
T Cell Lines ◽  
Myelin Antigens

Multiple sclerosis (MS) is an autoimmune disease where T-cells activated against myelin antigens are involved in myelin destruction. Yet, healthy subjects also harbor T-cells responsive to myelin antigens, suggesting that MS patient-derived autoimmune T-cells might bear functional differences from T-cells derived from healthy individuals. We addressed this issue by analyzing gene expression patterns of myelin oligodendrocytic glycoprotein (MOG) responsive T-cell lines generated from MS patients and healthy subjects. We identified 150 transcripts that were differentially expressed between MS patients and healthy controls. The most informative 43 genes exhibited >1.5-fold change in expression level. Eighteen genes were up-regulated including BCL2, lifeguard, IGFBP3 and VEGF. Twenty five genes were down-regulated, including apoptotic activators like TNF and heat shock protein genes. This gene expression pattern was unique to MOG specific T-cell lines and was not expressed in T-cell lines reactive to tetanus toxin (TTX). Our results indicate that activation in MS that promotes T-cell survival and expansion, has its own state and that the unique gene expression pattern that characterize autoreactive T-cells in MS represent a constellation of factors in which the chronicity, timing and accumulation of damage make the difference between health and disease.

scholarly journals Ovine herpesvirus 2 lytic cycle replication and capsid production

2002 ◽  
Vol 83 (12) ◽  
pp. 2999-3002 ◽  
Author(s):  
Jane Rosbottom ◽  
Robert G. Dalziel ◽  
Hugh W. Reid ◽  
James P. Stewart
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Cell Lines ◽  
Lytic Cycle ◽  
Malignant Catarrhal Fever ◽  
Virus Capsids ◽  
Latently Infected ◽  
T Cell Lines ◽  
First Time

Ovine herpesvirus 2 (OvHV-2) causes malignant catarrhal fever in cattle, pigs and deer. We have observed intact circular and linear OvHV-2 genomes in infected T cell lines derived from cows and rabbits. Bovine T cell lines were predominantly latently infected but rabbit T cell lines supported OvHV-2 productive cycle gene expression and virus capsids were demonstrated for the first time.

scholarly journals Functionally restricted, allospecific, human helper T cell lines that amplify either B cell or cytolytic T cell responses.

1983 ◽  
Vol 157 (5) ◽  
pp. 1675-1680 ◽  
Author(s):  
S M Friedman ◽  
G S Thompson
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Cell Lines ◽  
Cytotoxic T Lymphocytes ◽  
The Other ◽  
Helper T Cells ◽  
Cell Responses ◽  
Histocompatibility Complex ◽  
Human T Cell ◽  
T Cell Lines

Using a panel of partially cloned, OKT4+, DRw-1-specific, alloproliferative human T cell lines, we have identified two functionally restricted and reciprocating types of helper T cells. One provides major histocompatibility complex-restricted help for plaque-forming cell responses by DRw 1+ allogeneic B cells; the other preferentially amplifies the generation of allospecific cytotoxic T lymphocytes (CTL) from CTL precursors that have been suboptimally triggered by alloantigen.

Serial analysis of gene expression in HIV-1-infected T cell lines

FEBS Letters ◽  
1999 ◽  
Vol 462 (1-2) ◽  
pp. 182-186 ◽  
Author(s):  
Akihide Ryo ◽  
Youichi Suzuki ◽  
Kouji Ichiyama ◽  
Toru Wakatsuki ◽  
Nobuo Kondoh ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Cell Lines ◽  
T Cell Lines ◽  
Hiv 1
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