TY  - JOUR
AU  - Ugrin, Milena
AU  - Zukić, Branka
AU  - Stojiljković, Maja
AU  - Bartsakoulia, Marina
AU  - Stanković, Biljana
AU  - Kotur, Nikola
AU  - Dokmanović, Lidija
AU  - Georgitsi, Marianthi
AU  - Patrinos, George P.
AU  - Pavlović, Sonja
PY  - 2013
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/617
AB  - Hereditary persistence of fetal hemoglobin (HPFH) is a rare hereditary condition resulting in elevated levels of fetal hemoglobin (HbF) in adults. Typical HPFH is associated with promoter mutations or large deletions affecting the human fetal globin (HBG1 and HBG2) genes, while genetic defects in other genes involved in human erythropoiesis, e.g. KLF1, also result in atypical HPFH. Here, we report the first KLF1 gene promoter mutation (KLF1:g.-148G  gt  A) that is associated with increased HbF level. This mutation was shown to result in drastically reduced CAT reporter gene expression in K562 cells, compared to the wild-type sequence (p = 0.009) and also in reduced KLF1 gene expression in vivo. Furthermore, consistent with in silico analysis, electrophoretic mobility shift analysis showed that the KLF1:g.-148G  gt  A mutation resides in a Sp1 binding site and further that this mutation leads to the ablation of Sp1 binding in vitro. These data suggest that the KLF1:g-148G  gt  A mutation could play a role in increasing HbF levels in adults and further underlines the role of KLF1 as one of the key transcription factors involved in human fetal globin gene switching.
PB  - Springer, New York
T2  - Annals of Hematology
T1  - Functional analysis of a novel KLF1 gene promoter variation associated with hereditary persistence of fetal hemoglobin
EP  - 58
IS  - 1
SP  - 53
VL  - 92
DO  - 10.1007/s00277-012-1625-9
ER  - 

@article{
author = "Ugrin, Milena and Zukić, Branka and Stojiljković, Maja and Bartsakoulia, Marina and Stanković, Biljana and Kotur, Nikola and Dokmanović, Lidija and Georgitsi, Marianthi and Patrinos, George P. and Pavlović, Sonja",
year = "2013",
abstract = "Hereditary persistence of fetal hemoglobin (HPFH) is a rare hereditary condition resulting in elevated levels of fetal hemoglobin (HbF) in adults. Typical HPFH is associated with promoter mutations or large deletions affecting the human fetal globin (HBG1 and HBG2) genes, while genetic defects in other genes involved in human erythropoiesis, e.g. KLF1, also result in atypical HPFH. Here, we report the first KLF1 gene promoter mutation (KLF1:g.-148G  gt  A) that is associated with increased HbF level. This mutation was shown to result in drastically reduced CAT reporter gene expression in K562 cells, compared to the wild-type sequence (p = 0.009) and also in reduced KLF1 gene expression in vivo. Furthermore, consistent with in silico analysis, electrophoretic mobility shift analysis showed that the KLF1:g.-148G  gt  A mutation resides in a Sp1 binding site and further that this mutation leads to the ablation of Sp1 binding in vitro. These data suggest that the KLF1:g-148G  gt  A mutation could play a role in increasing HbF levels in adults and further underlines the role of KLF1 as one of the key transcription factors involved in human fetal globin gene switching.",
publisher = "Springer, New York",
journal = "Annals of Hematology",
title = "Functional analysis of a novel KLF1 gene promoter variation associated with hereditary persistence of fetal hemoglobin",
pages = "58-53",
number = "1",
volume = "92",
doi = "10.1007/s00277-012-1625-9"
}

Ugrin, M., Zukić, B., Stojiljković, M., Bartsakoulia, M., Stanković, B., Kotur, N., Dokmanović, L., Georgitsi, M., Patrinos, G. P.,& Pavlović, S.. (2013). Functional analysis of a novel KLF1 gene promoter variation associated with hereditary persistence of fetal hemoglobin. in Annals of Hematology
Springer, New York., 92(1), 53-58.
https://doi.org/10.1007/s00277-012-1625-9

Ugrin M, Zukić B, Stojiljković M, Bartsakoulia M, Stanković B, Kotur N, Dokmanović L, Georgitsi M, Patrinos GP, Pavlović S. Functional analysis of a novel KLF1 gene promoter variation associated with hereditary persistence of fetal hemoglobin. in Annals of Hematology. 2013;92(1):53-58.
doi:10.1007/s00277-012-1625-9 .

Ugrin, Milena, Zukić, Branka, Stojiljković, Maja, Bartsakoulia, Marina, Stanković, Biljana, Kotur, Nikola, Dokmanović, Lidija, Georgitsi, Marianthi, Patrinos, George P., Pavlović, Sonja, "Functional analysis of a novel KLF1 gene promoter variation associated with hereditary persistence of fetal hemoglobin" in Annals of Hematology, 92, no. 1 (2013):53-58,
https://doi.org/10.1007/s00277-012-1625-9 . .