Control of globin gene expression during development and erythroid differentiation

Stamatoyannopoulos, George

doi:10.1016/j.exphem.2004.11.007

Cited by 360 publications

(347 citation statements)

References 86 publications

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“…[10][11][12][13] The cause of this variability is poorly understood. 11,12,29,30 HbF concentration in blood is determined by interactions among chromosome remodeling activities, transcription factors, genes modulating erythropoiesis, genetic elements linked to the b-globin gene cluster, the kinetics of erythroid cell differentiation and differential red cell survival (for reviews see Bank 31 and Stamatoyannopoulos 32 ). This complex regulatory environment provides ample opportunity for genetic modulation of HbF production.…”

Section: Discussionmentioning

confidence: 99%

Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea

et al. 2007

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The increase in fetal hemoglobin (HbF) in response to hydroxyurea (HU) varies among patients with sickle cell anemia. Twenty-nine candidate genes within loci previously reported to be linked to HbF level (6q22.3-q23.2, 8q11-q12 and Xp22.2-p22.3), involved in metabolism of HU and related to erythroid progenitor proliferation were studied in 137 sickle cell anemia patients treated with HU. Three-hundred and twenty tagging single nucleotide polymorphisms (SNPs) for genotyping were selected based on HapMap data. Multiple linear regression and the nonlinear regression Random Forest method were used to investigate the association between SNPs and the change in HbF level after 2 years of treatment with HU. Both methods revealed that SNPs in genes within the 6q22.3-23.2 and 8q11-q12 linkage peaks, and also the ARG2, FLT1, HAO2 and NOS1 genes were associated with the HbF response to HU. Polymorphisms in genes regulating HbF expression, HU metabolism and erythroid progenitor proliferation might modulate the patient response to HU.

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Section: Discussionmentioning

confidence: 99%

Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea

et al. 2007

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“…In this study, we demonstrate that transgenic MCF7 cells induced to over-express HMGA1 proteins (i.e., "ON" cells) exhibit compromised nucleotide excision repair of UV-induced photoproducts both in a constitutively active HPRT gene allele (which exists in a more "open" or accessible chromatin structure; [8]) and the silent β-globin gene (which exists in a "closed", or compacted, chromatin structure; [11]) compared to non-HMGA1-expressing "OFF" cells. While repair of both gene loci was significantly inhibited in the presence of HMGA1 proteins, this effect was much more pronounced in the transcriptionally silent β-globin gene.…”

Section: Discussionmentioning

confidence: 88%

“…Utilizing a recently developed quantitative long-range PCR-based assay for measuring genespecific removal of UV-induced lesions [7], we assessed the efficiency of removal of UVinduced DNA damage in two different human genes: the hypoxanthine phosphoribosyl transferase (HPRT) gene, an allele of which is constitutively expressed in all normal somatic cells [8][9][10]), and the β-globin gene, which is transcriptionally silent in all cells but those of erythroid lineage [11]. These genes were chosen because microarray and other analyses indicated that HMGA1 proteins do not regulate the transcription of either gene in the cell lines being investigated (unpublished data), an important consideration given that these proteins can either positively or negatively regulate the transcription of a large number of genes in vivo (reviewed in: [12]).…”

Section: Introductionmentioning

confidence: 99%

Gene-specific nucleotide excision repair is impaired in human cells expressing elevated levels of high mobility group A1 nonhistone proteins

et al. 2007

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Previous work has established that stably-transfected human MCF7 cells over-expressing high mobility group A1 proteins (HMGA1) are deficient in global genomic repair (GGR) following exposure to either UV light or cisplatin. To investigate whether HMGA1 over-expression also interferes with gene-specific repair, we employed a rapid and convenient quantitative polymerase chain reaction assay for measuring repair in unique DNA sequences. Efficiency of UV-induced lesion removal was assessed for two genes in MCF7 cells either induced, or not, to over-express transgenic HMGA1 proteins: the constitutively active HPRT gene and the transcriptionally silent β-globin gene. As controls, similar experiments were also performed in non-transgenic MCF7 cells that do not express detectable levels of HMGA1 and in normal human embryonic fibroblasts that naturally overexpress HMGA1 proteins. Our results indicate that exposure of cells to a UV dose of 20 J/m 2 produced an average of 0.21 ± 0.03 lesions/kb and 0.19 ± 0.02 lesions/kb in the HPRT and β-globin genes, respectively, with no significant difference between HMGA1 over-expressing cells and nonexpressing cells. On the other hand, analysis of repair following UV exposure revealed that, compared to controls, HMGA1 over-expressing cells take considerably longer to repair photo-lesions in both the active HPRT and the silent β-globin loci, with non-expressing cells repairing 50% of lesions in HPRT 3-4 hours faster than HMGA1 over-expressing cells. Interestingly, the delay in repair is even more prolonged in the silent β-globin locus in HMGA1 over-expressing cells compared to control cells. To our knowledge, this is the first report of HMGA1 proteins inhibiting NER within specific genes located in either transcriptionally active "open", or inactive "closed", chromatin domains. Furthermore, taken together with previous findings, these results suggest that HMGA1 overexpression interferes with repair processes common to both the GGR and transcription coupled repair pathways.

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“…However, nobody paid attention to this gene in the field of 'cancer'. Even physiologically, HBB expression is controlled intricately (Stamatoyannopoulos, 2005). In the viewpoint of cancer genetics, it strongly required further examination of the mechanism of the downregulation of HBB in anaplastic thyroid cancer.…”

Section: Discussionmentioning

confidence: 99%

Decreased expression of haemoglobin beta (HBB) gene in anaplastic thyroid cancer and recovory of its expression inhibits cell growth

et al. 2005

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Anaplastic thyroid cancer (ATC) is one of the most fulminant and foetal diseases in human malignancies. However, the genetic alterations and carcinogenic mechanisms of ATC are still unclear. Recently, we investigated the gene expression profile of 11 anaplastic thyroid cancer cell lines (ACL) and significant decreased expression of haemoglobin beta (HBB) gene in ACL. Haemoglobin beta is located at 11p15.5, where loss of heterozygosity (LOH) was reported in various kinds of cancers, including ATC, and it has been suggested that novel tumour suppressor genes might exist in this region. In order to clarify the meaning of decreased expression of HBB in ATC, the expression status of HBB was investigated with ACL, ATC, papillary thyroid cancer (PTC) and normal human tissues. Haemoglobin beta showed significant decreased expression in ACLs and ATCs; however, in PTC, HBB expressed equal to the normal thyroid gland. In addition, HBB expressed in normal human tissues ubiquitously. To validate the tumour-suppressor function of HBB, cell growth assay was performed. Forced expression of HBB in KTA2 cell, which is a kind of ACL, significantly suppressed KTA2 growth. The mechanism of downregulation of HBB in ATC is still unclear; however, our results suggested the possibility of HBB as a novel tumour-suppressor gene.

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Control of globin gene expression during development and erythroid differentiation

Abstract: Extensive studies during the

Cited by 360 publications

References 86 publications

Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea

Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea

Gene-specific nucleotide excision repair is impaired in human cells expressing elevated levels of high mobility group A1 nonhistone proteins

Decreased expression of haemoglobin beta (HBB) gene in anaplastic thyroid cancer and recovory of its expression inhibits cell growth

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