β-thalassemia intermedia due to compound heterozygosity for two β-globin gene promoter mutations, including a novel TATA box deletion

2007 ◽  
Vol 50 (2) ◽  
pp. 363-366 ◽  
Author(s):  
Raveen K. Basran ◽  
Ulrike M. Reiss ◽  
Hong-yuan Luo ◽  
Russell E. Ware ◽  
David H.K. Chui
Keyword(s):  
Globin Gene ◽  
Gene Promoter ◽  
Tata Box ◽  
Compound Heterozygosity ◽  
Thalassemia Intermedia ◽  
Promoter Mutations

scholarly journals β-Thalassaemia Major in a Spanish Patient due to a Compound Heterozygosity for CD39C→T/−28A→C

2009 ◽  
Vol 2009 ◽  
pp. 1-3 ◽  
Author(s):  
Soledad Gamarra ◽  
Guillermo Garcia-Effron ◽  
Carmen Monteserin ◽  
Isabel Lopez-Villar ◽  
Florinda Gilsanz ◽  
...  
Keyword(s):  
Male Patient ◽  
Globin Gene ◽  
Gene Mutations ◽  
Gene Promoter ◽  
Tata Box ◽  
Spanish Population ◽  
Compound Heterozygosity ◽  
Thalassaemia Major ◽  
Spanish Patient ◽  
First Report

A Spanish male patient withβ-thalassaemia major was studied. Compound heterozygosity was found for one of the most commonβ-globin gene mutations in the Spanish population (codon 39C→T) and for a mutation in the TATA box element of theβ-globin gene promoter (−28 A→Cmutation). To our knowledge this is the first report of a CD39C→Tand−28 A→Cchange association and the first report of the−28 A→Csubstitution in a Spanish patient.

scholarly journals Structural and Functional Cross-Talk between a Distant Enhancer and the ɛ-Globin Gene Promoter Shows Interdependence of the Two Elements in Chromatin

1999 ◽  
Vol 19 (11) ◽  
pp. 7600-7609 ◽  
Author(s):  
Jennifer C. McDowell ◽  
Ann Dean
Keyword(s):  
Globin Gene ◽  
Gene Promoter ◽  
Transcription Activation ◽  
Tata Box ◽  
Globin Genes ◽  
Hypersensitive Site ◽  
Nuclease Digestion ◽  
Dnase I Hypersensitive Site ◽  
Globin Promoter ◽  
Gata Motif

ABSTRACT We investigated the requirements for enhancer-promoter communication by using the human β-globin locus control region (LCR) DNase I-hypersensitive site 2 (HS2) enhancer and the ɛ-globin gene in chromatinized minichromosomes in erythroid cells. Activation of globin genes during development is accompanied by localized alterations of chromatin structure, and CACCC binding factors and GATA-1, which interact with both globin promoters and the LCR, are believed to be critical for globin gene transcription activation. We found that an HS2 element mutated in its GATA motif failed to remodel the ɛ-globin promoter or activate transcription yet HS2 nuclease accessibility did not change. Accessibility and transcription were reduced at promoters with mutated GATA-1 or CACCC sites. Strikingly, these mutations also resulted in reduced accessibility at HS2. In the absence of a globin gene, HS2 is similarly resistant to nuclease digestion. In contrast to observations in Saccharomyces cerevisiae, HS2-dependent promoter remodeling was diminished when we mutated the TATA box, crippling transcription. This mutation also reduced HS2 accessibility. The results indicate that the ɛ-globin promoter and HS2 interact both structurally and functionally and that both upstream activators and the basal transcription apparatus contribute to the interaction. Further, at least in this instance, transcription activation and promoter remodeling by a distant enhancer are not separable.

Three New β-Globin Gene Promoter Mutations Identified Through Newborn Screening

Hemoglobin ◽  
2007 ◽  
Vol 31 (2) ◽  
pp. 129-134 ◽  
Author(s):  
Barry Eng ◽  
Lynda Walker ◽  
Lisa M. Nakamura ◽  
Carolyn Hoppe ◽  
Mahin Azimi ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Globin Gene ◽  
Gene Promoter ◽  
Promoter Mutations

B Locus YAC Mice Carrying G Gene Promoter Mutations: Insights into the Mechanism of Action of the -175 HPFH Mutation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1225-1225
Author(s):  
Man Yu ◽  
Xin Ye ◽  
Hemei Han ◽  
Mary Stafford ◽  
Patrick A. Navas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transgenic Mice ◽  
Globin Gene ◽  
Rnase Protection Assay ◽  
Gene Activation ◽  
Gene Promoter ◽  
Wild Type ◽  
Rnase Protection ◽  
Gene Reactivation ◽  
Promoter Mutations

Abstract Non-deletional HPFHs are g gene promoter mutations, which are associated with HbF elevation in heterozygous adult individuals. To investigate the mechanism whereby these mutations result in g gene activation, the −198 (T→C) and −175 (T→C) mutations were introduced into the promoter of the Ag gene in the context of a 213 kb b-globin locus YAC. The mutated YAC DNA was then used to produce transgenic mice. Expression of the human g and b globin gene was examined by RNase protection assay in blood of the adult transgenic mice carrying either −198 or −175 mutations. The level of g gene expression ranged from 4.0 to 8.5% of the human b mRNA in the −198 mutant transgenic mice, and from 25 to 41% in the −175 mutant mice. In contrast, there was no detectable level of g gene expression in the blood of wild type transgenic mice. The ratios of g/b mRNA in the mutant transgenic mice correspond to the levels of Hb F in adult individuals carrying the corresponding mutations: Hb F in heterozygotes for HPFH −198 and −175 mutations ranges from 3.5 to 10% and from 36 to 41%, respectively. To delineate the mechanism of g gene reactivation by the HPFH mutations, the CACCC box in the g gene promoter was deleted in the context of the mutant YAC. In contrast to the −175 HPFH bYAC mice, in the doubly mutated −175 HPFH DAgCACCC bYAC mice, expression of the g gene in the adult blood of the transgenic mice was undetectable. These results provide strong evidence that an intact CACCC box is required for g gene activation in the −175 HPFH mutation. We conclude that YAC mice can faithfully reproduce the phenotypes of nondeletional HPFH mutations and be used for the investigation of the mechanisms by which these mutations activate the g gene.

Effect of TATA Box polymorphisms in human β-globin gene promoter associated with β-thalassemia on interaction with TATA-binding protein

2011 ◽  
Vol 1 (3) ◽  
pp. 183-188 ◽  
Author(s):  
I. A. Drachkova ◽  
T. V. Arshinova ◽  
P. M. Ponomarenko ◽  
T. I. Merkulova ◽  
N. A. Kolchanov ◽  
...  
Keyword(s):  
Binding Protein ◽  
Globin Gene ◽  
Gene Promoter ◽  
Tata Binding Protein ◽  
Tata Box

scholarly journals Nuclear factor I (NF I) binds to an NF I-type site but not to the CCAAT site in the human alpha-globin gene promoter.

1992 ◽  
Vol 267 (12) ◽  
pp. 8478-8484 ◽  
Author(s):  
H Zorbas ◽  
T Rein ◽  
A Krause ◽  
K Hoffmann ◽  
E.L. Winnacker
Keyword(s):  
Globin Gene ◽  
Gene Promoter ◽  
Nuclear Factor ◽  
Factor I ◽  
Alpha Globin ◽  
Nuclear Factor I ◽  
Type Site
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