scholarly journals Alpha-thalassemia resulting from deletion of regulatory sequences far upstream of the alpha-globin structural genes

Blood ◽  
1991 ◽  
Vol 78 (6) ◽  
pp. 1589-1595
Author(s):  
L Romao ◽  
L Osorio-Almeida ◽  
DR Higgs ◽  
J Lavinha ◽  
SA Liebhaber
Keyword(s):  
Gene Expression ◽  
Transcription Start Site ◽  
Globin Gene ◽  
Regulatory Sequences ◽  
Start Site ◽  
Structural Genes ◽  
Transcription Start ◽  
Alpha Thalassemia ◽  
Alpha Globin ◽  
Globin Gene Expression

We describe an alpha-thalassemia determinant in which alpha-globin expression is silenced by a deletion located 27 kb 5′ to the transcription start site of the alpha 2-globin gene. This alpha- thalassemic determinant, (alpha alpha)MM, is a member of a newly described group of thalassemic mutations resulting from deletion of locus-controlling sequences critical to globin gene expression.

scholarly journals Alpha-thalassemia resulting from deletion of regulatory sequences far upstream of the alpha-globin structural genes

Blood ◽  
1991 ◽  
Vol 78 (6) ◽  
pp. 1589-1595 ◽  
Author(s):  
L Romao ◽  
L Osorio-Almeida ◽  
DR Higgs ◽  
J Lavinha ◽  
SA Liebhaber
Keyword(s):  
Gene Expression ◽  
Transcription Start Site ◽  
Globin Gene ◽  
Regulatory Sequences ◽  
Start Site ◽  
Structural Genes ◽  
Transcription Start ◽  
Alpha Thalassemia ◽  
Alpha Globin ◽  
Globin Gene Expression

Abstract We describe an alpha-thalassemia determinant in which alpha-globin expression is silenced by a deletion located 27 kb 5′ to the transcription start site of the alpha 2-globin gene. This alpha- thalassemic determinant, (alpha alpha)MM, is a member of a newly described group of thalassemic mutations resulting from deletion of locus-controlling sequences critical to globin gene expression.

scholarly journals Human embryonic zeta-globin gene expression in mouse-human hybrid erythroid cell lines

Blood ◽  
1995 ◽  
Vol 86 (3) ◽  
pp. 1212-1217 ◽  
Author(s):  
HY Luo ◽  
AB Deisseroth ◽  
DH Chui
Keyword(s):  
Gene Expression ◽  
Globin Gene ◽  
Erythroid Cell ◽  
Hybrid Cells ◽  
Globin Chains ◽  
Alpha Thalassemia ◽  
Alpha Globin ◽  
Zeta Globin Gene ◽  
Murine Erythroleukemia ◽  
Globin Gene Expression

Abstract The human alpha-globin-like embryonic zeta-globin chains are present in abundance during the first 5 to 6 weeks of gestation. Subsequently, zeta-globin chains are present in fetal blood at a very low level, which is supplanted by the expression of alpha-globin chains. Adult individuals who are carriers of the (--SEA/) alpha-thalassemia deletion, in contrast to normal adults, have low levels of embryonic zeta-globin chains in their circulating erythrocytes. In this investigation, we constructed stable mouse-human hybrid cells with murine erythroleukemia cells bearing human chromosome 16, with either the normal alpha-globin gene cluster (alpha alpha/) or the (--SEA/) type of alpha-thalassemia deletion. The results on the human zeta- globin gene expression in these hybrid cells indicate that murine adult erythroid transcription factors can induce the expression of human embryonic zeta-globin gene is cis to the (--SEA/) deletion, in parallel with the endogenous mouse alpha-globin gene expression. These data also show the importance of the DNA sequences within the (--SEA) deletion in regulating the expression of zeta-globin gene in cis during normal human hemoglobin ontogeny.

scholarly journals Distinct Viral Sequence Elements Are Necessary for Expression of Tomato golden mosaic virus Complementary Sense Transcripts That Direct AL2 and AL3 Gene Expression

2006 ◽  
Vol 19 (12) ◽  
pp. 1394-1405 ◽  
Author(s):  
Chia-Yi Shung ◽  
Janet Sunter ◽  
Shyam S. Sirasanagandla ◽  
Garry Sunter
Keyword(s):  
Gene Expression ◽  
Mosaic Virus ◽  
Transcription Start Site ◽  
Transcription Initiation ◽  
Regulatory Sequences ◽  
Tomato Golden Mosaic Virus ◽  
Start Site ◽  
Suspension Cells ◽  
Transcription Start ◽  
Complementary Sense

Transient expression studies using Nicotiana benthamiana protoplasts and plants have identified sequences important for transcription of complementary sense RNAs derived from Tomato golden mosaic virus (TGMV) DNA component A that direct expression of AL2 and AL3. Transcription of two complementary sense RNAs, initiating at nucleotides 1,935 (AL1935) and 1,629 (AL1629), is directed by unique sequences located upstream of each transcription initiation site. One element is located between 28 and 124 nucleotides (nt) upstream of the AL1935 transcription start site, which differs from a second element located 150 nt downstream, between 129 and 184 nt upstream of the AL1629 transcription start site. Transcription initiation at nucleotide 1,935 is lower than that at nucleotide 1,629 as determined by run-on transcription assays, and the resulting transcript is only capable of expressing AL3. The transcript initiating at nucleotide 1,629 is capable of directing expression of both AL2 and AL3, although expression of AL3 is up to fourfold greater than that for AL2. Nuclear factors purified from tobacco suspension cells bind to sequences upstream of both AL1935 and AL1629, correlating with the ability of these sequences to direct gene expression. Thus, in tobacco, regulatory sequences direct transcription of two unique TGMV messenger RNAs that differentially express AL2 and AL3.

scholarly journals Human embryonic zeta-globin gene expression in mouse-human hybrid erythroid cell lines

Blood ◽  
1995 ◽  
Vol 86 (3) ◽  
pp. 1212-1217 ◽  
Author(s):  
HY Luo ◽  
AB Deisseroth ◽  
DH Chui
Keyword(s):  
Gene Expression ◽  
Globin Gene ◽  
Erythroid Cell ◽  
Hybrid Cells ◽  
Globin Chains ◽  
Alpha Thalassemia ◽  
Alpha Globin ◽  
Zeta Globin Gene ◽  
Murine Erythroleukemia ◽  
Globin Gene Expression

The human alpha-globin-like embryonic zeta-globin chains are present in abundance during the first 5 to 6 weeks of gestation. Subsequently, zeta-globin chains are present in fetal blood at a very low level, which is supplanted by the expression of alpha-globin chains. Adult individuals who are carriers of the (--SEA/) alpha-thalassemia deletion, in contrast to normal adults, have low levels of embryonic zeta-globin chains in their circulating erythrocytes. In this investigation, we constructed stable mouse-human hybrid cells with murine erythroleukemia cells bearing human chromosome 16, with either the normal alpha-globin gene cluster (alpha alpha/) or the (--SEA/) type of alpha-thalassemia deletion. The results on the human zeta- globin gene expression in these hybrid cells indicate that murine adult erythroid transcription factors can induce the expression of human embryonic zeta-globin gene is cis to the (--SEA/) deletion, in parallel with the endogenous mouse alpha-globin gene expression. These data also show the importance of the DNA sequences within the (--SEA) deletion in regulating the expression of zeta-globin gene in cis during normal human hemoglobin ontogeny.

scholarly journals Sequence of the 5′-flanking region and promoter activity of the human mucin gene MUC5B in different phenotypes of colon cancer cells

2000 ◽  
Vol 348 (3) ◽  
pp. 675-686 ◽  
Author(s):  
Isabelle VAN SEUNINGEN ◽  
Michaël PERRAIS ◽  
Pascal PIGNY ◽  
Nicole PORCHET ◽  
Jean-Pierre AUBERT
Keyword(s):  
Gene Expression ◽  
Transcription Start Site ◽  
Promoter Activity ◽  
Luciferase Reporter ◽  
Nuclear Factor ◽  
Start Site ◽  
Transcription Start ◽  
Mucin Gene ◽  
Intron 1 ◽  
Flanking Region

Control of gene expression in intestinal cells is poorly understood. Molecular mechanisms that regulate transcription of cellular genes are the foundation for understanding developmental and differentiation events. Mucin gene expression has been shown to be altered in many intestinal diseases and especially cancers of the gastrointestinal tract. Towards understanding the transcriptional regulation of a member of the 11p15.5 human mucin gene cluster, we have characterized 3.55 kb of the 5ʹ-flanking region of the human mucin gene MUC5B, including the promoter, the first two exons and the first intron. We report here the promoter activity of successively 5ʹ-truncated sections of 956 bases of this region by fusing it to the coding region of a luciferase reporter gene. The transcription start site was determined by primer-extension analysis. The region upstream of the transcription start site is characterized by the presence of a TATA box at bases -32/-26, DNA-binding elements for transcription factors c-Myc, N-Myc, Sp1 and nuclear factor ĸB as well as putative activator protein (AP)-1-, cAMP-response-element-binding protein (CREB)-, hepatocyte nuclear factor (HNF)-1-, HNF-3-, TGT3-, gut-enriched Krüppel factor (GKLF)-, thyroid transcription factor (TTF)-1- and glucocorticoid receptor element (GRE)-binding sites. Intron 1 of MUC5B was also characterized, it is 2511 nucleotides long and contains a DNA segment of 259 bp in which are clustered eight tandemly repeated GA boxes and a CACCC box that bind Sp1. AP-2α and GATA-1 nuclear factors were also shown to bind to their respective cognate elements in intron 1. In transfection studies the MUC5B promoter showed a cell-specific activity as it is very active in mucus-secreting LS174T cells, whereas it is inactive in Caco-2 enterocytes and HT-29 STD (standard) undifferentiated cells. Within the promoter, maximal transcription activity was found in a segment covering the first 223 bp upstream of the transcription start site. Finally, in co-transfection experiments a transactivating effect of Sp1 on to MUC5B promoter was seen in LS174T and Caco-2 cells.

scholarly journals Targeted inactivation of the major positive regulatory element (HS-40) of the human alpha-globin gene locus

Blood ◽  
1995 ◽  
Vol 86 (3) ◽  
pp. 1202-1211 ◽  
Author(s):  
A Bernet ◽  
S Sabatier ◽  
DJ Picketts ◽  
R Ouazana ◽  
F Morle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Locus ◽  
Regulatory Element ◽  
Globin Gene ◽  
Marker Gene ◽  
Regulatory Elements ◽  
Target System ◽  
Flp Recombinase ◽  
Alpha Globin ◽  
Globin Gene Expression

Abstract We have examined the role of the major positive upstream regulatory element of the human alpha-globin gene locus (HS-40) in its natural chromosomal context. Using homologous recombination, HS-40 was replaced by a neo marker gene in a mouse erythroleukemia hybrid cell line containing a single copy of human chromosome 16. In clones from which HS-40 had been deleted, human alpha-globin gene expression was severely reduced, although basal levels of alpha 1 and alpha 2-globin mRNA expression representing less than 3% of the level in control cell lines were detected. Deletion of the neo marker gene, by using FLP recombinase/FLP recombinase target system, proved that the phenotype observed was not caused by the regulatory elements of this marker gene. In the targeted clones, deletion of HS-40 apparently does not affect long-range or local chromatin structure at the alpha promoters. Therefore, these results indicate that, in the experimental system used, HS-40 behaves as a strong inducible enhancer of human alpha- globin gene expression.

scholarly journals Association ofXmnI Polymorphism and Hemoglobin E Haplotypes on Postnatal Gamma Globin Gene Expression in Homozygous Hemoglobin E

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Supachai Ekwattanakit ◽  
Yuwarat Monteerarat ◽  
Suchada Riolueang ◽  
Kalaya Tachavanich ◽  
Vip Viprakasit
Keyword(s):  
Gene Expression ◽  
Globin Gene ◽  
Laboratory Data ◽  
Regulatory Sequences ◽  
Chromosome 11 ◽  
Hemoglobin E ◽  
Association Analyses ◽  
Gamma Globin ◽  
Hb E ◽  
Globin Gene Expression

Background and Objectives. To explore the role ofcis-regulatory sequences within theβglobin gene cluster at chromosome 11 on humanγglobin gene expression related to Hb E allele, we analyze baseline hematological data and Hb F values together withβglobin haplotypes in homozygous Hb E.Patients and Methods. 80 individuals with molecularly confirmed homozygous Hb E were analyzed for theβglobin haplotypes andXmnI polymorphism using PCR-RFLPs. 74 individuals with complete laboratory data were further studied for association analyses.Results. Eight differentβglobin haplotypes were found linked to Hb E alleles; three major haplotypes were (a) (III), (b) (V), and (c) (IV) accounting for 94% of Hb E chromosomes. A new haplotype (Th-1) was identified and most likely converted from the major ones. The majority of individuals had Hb F < 5%; only 10.8% of homozygous Hb E had high Hb F (average 10.5%, range 5.8–14.3%). No association was found on a specific haplotype orXmnI in these individuals with high Hb F, measured by alkaline denaturation. Conclusion. The cis-regulation ofγglobin gene expression might not be apparent under a milder condition with lesser globin imbalance such as homozygous Hb E.

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