The distal β‐globin CACCC box is required for maximal stimulation of the β‐globin gene by EKLF

Summary The transcription factor erythroid Kruppel‐like factor (EKLF) specifically activates the β‐globin gene by interacting with the proximal β‐globin CACCC box, a known hot spot for thalassaemia mutations. This study investigated whether EKLF could also bind to, and activate from, the distal CACC...

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Vydáno v:	British journal of haematology Ročník 127; číslo 1; s. 114 - 117
Hlavní autoři:	Marini, Maria Giuseppina, Asunis, Isadora, Porcu, Loredana, Salgo, Maria Giulia, Loi, Maria Giuseppina, Brucchietti, Arianna, Cao, Antonio, Moi, Paolo
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Oxford, UK Blackwell Science Ltd 01.10.2004 Blackwell
Témata:	Anemias. Hemoglobinopathies Animals beta-Thalassemia - genetics beta-Thalassemia - metabolism Biological and medical sciences Cell Line Diseases of red blood cells DNA mutation DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism DNA‐binding proteins ex vivo expression Gene Expression Regulation Globins - genetics Hematologic and hematopoietic diseases Humans Kruppel-Like Transcription Factors Medical sciences Mice Promoter Regions, Genetic transcription control Transcription Factors - genetics Transcription Factors - metabolism Transcriptional Activation β‐thalassaemia Hemoglobinopathy Hematology Transcription Beta-Peptide chain DNA binding protein Stimulation Hemopathy β-thalassaemia Genetic disease Globin Transcription factor EKLF transcription control Regulation(control) Hemolytic anemia Ex vivo Gene β-Thalassemia DNA Distal DNA mutation Genetics Mutation ex vivo expression DNA-binding proteins
ISSN:	0007-1048, 1365-2141
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Abstract	Summary The transcription factor erythroid Kruppel‐like factor (EKLF) specifically activates the β‐globin gene by interacting with the proximal β‐globin CACCC box, a known hot spot for thalassaemia mutations. This study investigated whether EKLF could also bind to, and activate from, the distal CACCC, which is a rare site of thalassaemia mutations. Using band shift and transient expression analysis with wild type, single and double CACCC mutants, we established that the distal CACCC box is weakly bound by EKLF, but, when mutated, significantly impairs EKLF‐dependent β‐globin stimulation. Thus, EKLF requires both CACCC boxes to maximally stimulate the β‐globin gene.
AbstractList	Summary The transcription factor erythroid Kruppel‐like factor (EKLF) specifically activates the β‐globin gene by interacting with the proximal β‐globin CACCC box, a known hot spot for thalassaemia mutations. This study investigated whether EKLF could also bind to, and activate from, the distal CACCC, which is a rare site of thalassaemia mutations. Using band shift and transient expression analysis with wild type, single and double CACCC mutants, we established that the distal CACCC box is weakly bound by EKLF, but, when mutated, significantly impairs EKLF‐dependent β‐globin stimulation. Thus, EKLF requires both CACCC boxes to maximally stimulate the β‐globin gene. The transcription factor erythroid Kruppel‐like factor (EKLF) specifically activates the β ‐globin gene by interacting with the proximal β ‐globin CACCC box, a known hot spot for thalassaemia mutations. This study investigated whether EKLF could also bind to, and activate from, the distal CACCC, which is a rare site of thalassaemia mutations. Using band shift and transient expression analysis with wild type, single and double CACCC mutants, we established that the distal CACCC box is weakly bound by EKLF, but, when mutated, significantly impairs EKLF‐dependent β ‐globin stimulation. Thus, EKLF requires both CACCC boxes to maximally stimulate the β ‐globin gene. The transcription factor erythroid Kruppel-like factor (EKLF) specifically activates the beta-globin gene by interacting with the proximal beta-globin CACCC box, a known hot spot for thalassaemia mutations. This study investigated whether EKLF could also bind to, and activate from, the distal CACCC, which is a rare site of thalassaemia mutations. Using band shift and transient expression analysis with wild type, single and double CACCC mutants, we established that the distal CACCC box is weakly bound by EKLF, but, when mutated, significantly impairs EKLF-dependent beta-globin stimulation. Thus, EKLF requires both CACCC boxes to maximally stimulate the beta-globin gene.The transcription factor erythroid Kruppel-like factor (EKLF) specifically activates the beta-globin gene by interacting with the proximal beta-globin CACCC box, a known hot spot for thalassaemia mutations. This study investigated whether EKLF could also bind to, and activate from, the distal CACCC, which is a rare site of thalassaemia mutations. Using band shift and transient expression analysis with wild type, single and double CACCC mutants, we established that the distal CACCC box is weakly bound by EKLF, but, when mutated, significantly impairs EKLF-dependent beta-globin stimulation. Thus, EKLF requires both CACCC boxes to maximally stimulate the beta-globin gene. The transcription factor erythroid Kruppel-like factor (EKLF) specifically activates the beta-globin gene by interacting with the proximal beta-globin CACCC box, a known hot spot for thalassaemia mutations. This study investigated whether EKLF could also bind to, and activate from, the distal CACCC, which is a rare site of thalassaemia mutations. Using band shift and transient expression analysis with wild type, single and double CACCC mutants, we established that the distal CACCC box is weakly bound by EKLF, but, when mutated, significantly impairs EKLF-dependent beta-globin stimulation. Thus, EKLF requires both CACCC boxes to maximally stimulate the beta-globin gene.
Author	Cao, Antonio Porcu, Loredana Asunis, Isadora Loi, Maria Giuseppina Moi, Paolo Salgo, Maria Giulia Marini, Maria Giuseppina Brucchietti, Arianna
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Cites_doi	10.1182/blood.V73.6.1705.1705 10.1128/MCB.13.5.2776 10.1182/blood.V73.2.601.601 10.1074/jbc.270.4.1955 10.1182/blood.V81.10.2818.2818 10.1006/geno.1997.5147 10.1016/S0021-9258(17)42283-6 10.1006/bcmd.2002.0550 10.1093/nar/9.23.6505 10.1093/nar/19.9.2499
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Keywords	Hemoglobinopathy Hematology Transcription Beta-Peptide chain DNA binding protein Stimulation Hemopathy β-thalassaemia Genetic disease Globin Transcription factor EKLF transcription control Regulation(control) Hemolytic anemia Ex vivo Gene β-Thalassemia DNA Distal DNA mutation Genetics Mutation ex vivo expression DNA-binding proteins
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Snippet	Summary The transcription factor erythroid Kruppel‐like factor (EKLF) specifically activates the β‐globin gene by interacting with the proximal β‐globin CACCC... The transcription factor erythroid Kruppel‐like factor (EKLF) specifically activates the β ‐globin gene by interacting with the proximal β ‐globin CACCC box, a... The transcription factor erythroid Kruppel-like factor (EKLF) specifically activates the beta-globin gene by interacting with the proximal beta-globin CACCC...
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SubjectTerms	Anemias. Hemoglobinopathies Animals beta-Thalassemia - genetics beta-Thalassemia - metabolism Biological and medical sciences Cell Line Diseases of red blood cells DNA mutation DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism DNA‐binding proteins ex vivo expression Gene Expression Regulation Globins - genetics Hematologic and hematopoietic diseases Humans Kruppel-Like Transcription Factors Medical sciences Mice Promoter Regions, Genetic transcription control Transcription Factors - genetics Transcription Factors - metabolism Transcriptional Activation β‐thalassaemia
Title	The distal β‐globin CACCC box is required for maximal stimulation of the β‐globin gene by EKLF
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