Erythroid-specific Inhibition of the tal-1 Intragenic Promoter Is Due to Binding of a Repressor to a Novel Silencer

Courtes, C.; Lecointe, Nathalie; Cam, Laurent Le; Baudoin, Florence; Sardet, Claude; Mathieu-Mahul, D.

doi:10.1074/jbc.275.2.949

Cited by 14 publications

(24 citation statements)

References 65 publications

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“…These data are consistent with previous DNaseI hypersensitive site mapping of the core region of the mouse Tal1 locus using Southern blotting techniques . Three elements known to direct Tal1 expression to the developing brain (+1, +3, and +23) and the +12 element, homologous to the human +14 TAL1 repressor (Courtes et al 2000), were not significantly enriched above the regional baseline in 416B cells. Enrichments were highly reproducible between both biological and technical replicates.…”

Section: Resultsmentioning

confidence: 96%

“…The region at ‫9מ‬ functions as an enhancer in hematopoietic cell lines , and the +40 region is active in the primitive erythroid lineage (Delabesse et al 2005). The mouse +12 region is homologous to the human +14 region, which has been identified as an TAL1 transcriptional repressor (Courtes et al 2000).…”

Section: Resultsmentioning

confidence: 99%

“…Promoters for each of the genes reside within highly conserved regions of DNA immediately 5Ј to the transcriptional start sites (Aplan et al 1990(Aplan et al , 1991. Tal1 has two promoters located 5Ј to the gene (promoter 1a and promoter 1b), and a further promoter within exon 4 (+7 relative to mouse promoter 1a) (Courtes et al 2000). Tal1 enhancers are also highly conserved (Göttgens et al 2000(Göttgens et al , 2001(Göttgens et al , 2002aChapman et al 2004).…”

Section: Resultsmentioning

confidence: 99%

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Identifying gene regulatory elements by genomic microarray mapping of DNaseI hypersensitive sites

Follows

Dhami²,

Göttgens³

et al. 2006

Genome Res.

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The identification of cis-regulatory elements is central to understanding gene transcription. Hypersensitivity of cis-regulatory elements to digestion with DNaseI remains the gold-standard approach to locating such elements. Traditional methods used to identify DNaseI hypersensitive sites are cumbersome and can only be applied to short stretches of DNA at defined locations. Here we report the development of a novel genomic array-based approach to DNaseI hypersensitive site mapping (ADHM) that permits precise, large-scale identification of such sites from as few as 5 million cells. Using ADHM we identified all previously recognized hematopoietic regulatory elements across 200 kb of the mouse T-cell acute lymphocytic leukemia-1 (Tal1) locus, and, in addition, identified two novel elements within the locus, which show transcriptional regulatory activity. We further validated the ADHM protocol by mapping the DNaseI hypersensitive sites across 250 kb of the human TAL1 locus in CD34 + primary stem/progenitor cells and K562 cells and by mapping the previously known DNaseI hypersensitive sites across 240 kb of the human ␣-globin locus in K562 cells. ADHM provides a powerful approach to identifying DNaseI hypersensitive sites across large genomic regions.

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Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Identifying gene regulatory elements by genomic microarray mapping of DNaseI hypersensitive sites

Follows

Dhami²,

Göttgens³

et al. 2006

Genome Res.

View full text Add to dashboard Cite

show abstract

“…Electrophoretic mobility shift assay (EMSA) Nuclear extracts were prepared as described previously (Courtes et al, 2000). Each 10 µl reaction mixture contained, 3 or 10 µg of nuclear extract, 10 mM Hepes (pH 7.8), 50 mM KCl, 2 mM MgCl2, 1 mM EDTA, 1 mM dithiothreitol, 0.5 µg of poly(dIdC) and 100,000 cpm of a 32 P-labeled double-stranded oligonucleotide probe containing the TAL-1 E-box sequence (5′-ACCTGAACAGATG-GTCGGCT-3′).…”

Section: Western Blot Analysismentioning

confidence: 99%

The bHLH TAL-1/SCL regulates endothelial cell migration and morphogenesis

Lazrak

Deleuze

Noël

et al. 2004

Journal of Cell Science

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The basic helix-loop-helix tal-1 gene (or scl), known for its fundamental role in embryonic and adult hematopoiesis in vertebrates, is also required for embryonic vascular remodeling. In adults, TAL-1 protein is undetectable in quiescent endothelium but it is present in newly formed vessels including tumoral vasculature, indicating its involvement in angiogenesis. Here, we demonstrate that TAL-1 expression is tightly regulated during in vitro angiogenesis: it is low during the initial step of migration and is upregulated during formation of capillary-like structures. We investigated whether ectopic expression of either wild-type TAL-1 or a dominant-negative mutant lacking the DNA-binding domain (Δ-bas) modulates the activity of human primary endothelial cells in the angiogenic processes of migration, proliferation and cell morphogenesis. Overexpression of either wild-type or Δ-bas TAL-1 affected chemotactic migration of primary endothelial cells without modifying their proliferative properties. Ectopic expression of wild-type TAL-1 accelerated the formation of capillary-like structures in vitro and, in vivo, enhanced vascularisation in mice (Matrigel implants) associated with a general enlargement of capillary lumens. Importantly, transduction of the mutant Δbas completely impaired in vitro angiogenesis and strongly inhibited vascularisation in mice. Taken together, our data show that TAL-1 modulates the angiogenic response of endothelial cells by stimulating cell morphogenesis and by influencing their behavior in migration. This study highlights the importance of TAL-1 regulation in postnatal vascular remodeling and provides the first physiological evidence that links TAL-1 activity to endothelial cell morphogenic processes.

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“…21,22 A third SCL promoter, termed promoter IV, has been recently identified; 23 it does not by itself display cell type specificity. 24 The basic HLH (bHLH) protein encoded by the SCL gene exists as two major isoforms; a 42 kDa full-length protein and a 22 kDa amino-truncated form resulting from differential mRNA splicing, both are phosphorylated on serine and localize to the nucleus. 25 The clonal amplification of hematopoietic cells from a pluripotent stem cell, particularly of cells belonging to the MK compartment and the possible pathogenic contribution of these latter in the promotion of bone marrow fibrosis in MMM, 26 led us to seek for the possible involvement of a deregulated expression of SCL in such an amplification of the CD34 þ progenitor population and its commitment to the MK lineage.…”

Section: Introductionmentioning

confidence: 99%

Altered transcription of the stem cell leukemia gene in myelofibrosis with myeloid metaplasia

et al. 2003

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An increased number of circulating CD34 þ hematopoietic progenitors with a prominent proliferation of the megakaryocytic (MK) population are the hallmarks of the myeloproliferation in myelofibrosis with myeloid metaplasia (MMM). Analyzing the potential contribution of the stem cell leukemia (SCL) gene in MMM myeloproliferation was doubly interesting for SCL is expressed both in primitive-uncommitted progenitor cells and erythroid/MK cells, its transcription differentially initiating from promoter 1b and 1a, respectively. Our results show that: (i) the expression of SCL transcript is increased in peripheral blood mononuclear cells (PBMCs) from patients; (ii) SCL gene transcription is altered in MMM CD34 þ progenitor cells sorted into CD34 þ CD41 þ and CD34 þ CD41 À subpopulations. Actually, in patients, SCL transcription initiated at promoter 1b is restricted to primitive CD34 þ CD41 À progenitor cells, while it is detectable in both cell subsets from healthy subjects; (iii) the full-length isoform of SCL protein is present in patients' CD34 þ cells and in PBMC; in the latter the SCL-expressing cells mainly belong to the MK lineage in which its sublocalization is both nuclear and cytoplasmic, which contrasts with the sole nuclear staining observed in normal MK cells. Our demonstration of altered expression and transcription of SCL in patients' hematopoietic cells emphasizes the possible contribution of this regulatory nuclear factor to the hematopoietic dysregulation, which is a feature of myelofibrosis with myeloid metaplasia.

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Erythroid-specific Inhibition of the tal-1 Intragenic Promoter Is Due to Binding of a Repressor to a Novel Silencer

Cited by 14 publications

References 65 publications

Identifying gene regulatory elements by genomic microarray mapping of DNaseI hypersensitive sites

Identifying gene regulatory elements by genomic microarray mapping of DNaseI hypersensitive sites

The bHLH TAL-1/SCL regulates endothelial cell migration and morphogenesis

Altered transcription of the stem cell leukemia gene in myelofibrosis with myeloid metaplasia

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