scholarly journals Inhibition of G9a methyltransferase stimulates fetal hemoglobin production by facilitating LCR/γ-globin looping

Blood ◽  
2015 ◽  
Vol 126 (5) ◽  
pp. 665-672 ◽  
Author(s):  
Ivan Krivega ◽  
Colleen Byrnes ◽  
Jaira F. de Vasconcellos ◽  
Y. Terry Lee ◽  
Megha Kaushal ◽  
...  
Keyword(s):  
Fetal Hemoglobin ◽  
Adult Human ◽  
Key Points ◽  
Protein Occupancy ◽  
Hemoglobin Production

Key Points The G9a methyltransferase inhibitor UNC0638 increased pancellular expression of HbF to levels greater than 30% in adult human erythroblasts. UNC0638 altered globin locus epigenetic status/protein occupancy favoring LCR interaction with fetal genes at the expense of adult genes.

scholarly journals EHMT1 and EHMT2 inhibition induces fetal hemoglobin expression

Blood ◽  
2015 ◽  
Vol 126 (16) ◽  
pp. 1930-1939 ◽  
Author(s):  
Aline Renneville ◽  
Peter Van Galen ◽  
Matthew C. Canver ◽  
Marie McConkey ◽  
John M. Krill-Burger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Locus ◽  
Globin Gene ◽  
Fetal Hemoglobin ◽  
Erythroid Cells ◽  
Adult Human ◽  
Key Points ◽  
Globin Gene Expression

Key Points EHMT1/2 inhibition increases human γ-globin and HbF expression, as well as mouse embryonic β-globin gene expression. EHMT1/2 inhibition decreases H3K9Me2 and increases H3K9Ac at the γ-globin gene locus in adult human erythroid cells.

scholarly journals LIN28B-mediated expression of fetal hemoglobin and production of fetal-like erythrocytes from adult human erythroblasts ex vivo

Blood ◽  
2013 ◽  
Vol 122 (6) ◽  
pp. 1034-1041 ◽  
Author(s):  
Y. Terry Lee ◽  
Jaira F. de Vasconcellos ◽  
Joan Yuan ◽  
Colleen Byrnes ◽  
Seung-Jae Noh ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
Human Blood ◽  
Ex Vivo ◽  
Fetal Hemoglobin ◽  
Adult Human ◽  
Key Points

Key Points LIN28B regulates HbF expression in erythroblasts that are cultured from umbilical cord and adult human blood. LIN28B expression manifested a more fetal-like phenotype among adult human erythroblasts.

scholarly journals Metformin induces FOXO3-dependent fetal hemoglobin production in human primary erythroid cells

Blood ◽  
2018 ◽  
Vol 132 (3) ◽  
pp. 321-333 ◽  
Author(s):  
Yankai Zhang ◽  
Alireza Paikari ◽  
Pavel Sumazin ◽  
Carly C. Ginter Summarell ◽  
Jacy R. Crosby ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Fetal Hemoglobin ◽  
Dependent Manner ◽  
Metformin Treatment ◽  
Erythroid Cells ◽  
Erythroid Progenitor ◽  
Functional Studies ◽  
Erythroid Progenitor Cells ◽  
Key Points ◽  
Hemoglobin Production

Key Points Functional studies in human primary erythroid progenitor cells support a role for FOXO3 in γ-globin regulation. Metformin treatment of human primary erythroid progenitor cells increases fetal hemoglobin in a partially FOXO3-dependent manner.

scholarly journals Eukaryotic initiation factor 2α phosphorylation mediates fetal hemoglobin induction through a post-transcriptional mechanism

Blood ◽  
2013 ◽  
Vol 122 (4) ◽  
pp. 477-485 ◽  
Author(s):  
Cynthia K. Hahn ◽  
Christopher H. Lowrey
Keyword(s):  
Fetal Hemoglobin ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Erythroid Progenitors ◽  
Eif2α Phosphorylation ◽  
Key Points ◽  
Pharmacologic Agents

Key PointsIncreasing eIF2α phosphorylation increases fetal hemoglobin in human primary erythroid progenitors via a post-transcriptional mechanism. Combining pharmacologic agents that use transcriptional and post-transcriptional mechanisms additively induces fetal hemoglobin.

Point mutation associated with hereditary persistence of fetal hemoglobin decreases RNA polymerase III transcription upstream of the affected gamma-globin gene

1986 ◽  
Vol 6 (9) ◽  
pp. 3278-3282
Author(s):  
D P Carlson ◽  
J Ross
Keyword(s):  
Rna Polymerase ◽  
Globin Gene ◽  
Rna Polymerase Iii ◽  
Fetal Hemoglobin ◽  
In Vitro Transcription ◽  
Base Substitution ◽  
Gamma Globin ◽  
Polymerase Iii ◽  
Hemoglobin Production

A base substitution in the 5'-flanking region of a human fetal globin gene is associated with abnormal fetal hemoglobin production. It also reduces by 5- to 10-fold in vitro transcription of the gene by RNA polymerase III. We discuss potential links between polymerase III transcription and abnormal hemoglobin production.

scholarly journals Inhibition of erythroblast growth and fetal hemoglobin production by ribofuranose-substituted adenosine derivatives

2008 ◽  
Vol 1782 (9) ◽  
pp. 504-510 ◽  
Author(s):  
Natarajan V. Bhanu ◽  
Y. Terry Lee ◽  
Patricia A. Oneal ◽  
Nicole M. Gantt ◽  
Wulin Aerbajinai ◽  
...  
Keyword(s):  
Fetal Hemoglobin ◽  
Adenosine Derivatives ◽  
Hemoglobin Production

scholarly journals High fetal hemoglobin production in sickle cell anemia in the eastern province of Saudi Arabia is genetically determined

Blood ◽  
1986 ◽  
Vol 67 (5) ◽  
pp. 1404-1410 ◽  
Author(s):  
BA Miller ◽  
M Salameh ◽  
M Ahmed ◽  
J Wainscoat ◽  
G Antognetti ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Fetal Hemoglobin ◽  
Cell Disease ◽  
Chromosome 11 ◽  
Eastern Province ◽  
Genetically Determined ◽  
Hemoglobin Production

Abstract Homozygous sickle cell disease in the eastern province of Saudi Arabia is clinically mild. Circulating fetal hemoglobin levels of 16.0 +/- 7.4% were found in these anemic patients, but only 1.09 +/- 0.97% in their sickle trait parents. To determine whether these sickle cell anemia patients inherit an increased capacity to synthesize fetal hemoglobin, a radioimmunoassay of fetal and adult hemoglobin was performed on erythroid progenitor (BFU-E)-derived erythroblasts from Saudi Arabian sickle cell patients and their parents. Mean fetal hemoglobin content per BFU-E-derived erythroblast from Saudi Arabian sickle cell patients was 6.2 +/- 2.4 pg/cell or 30.4 +/- 8.6% fetal hemoglobin (normal 1.1 +/- 0.7 pg/cell and 5.1 +/- 1.8%). Linear regression analysis of % HbF in peripheral blood versus % HbF per BFU-E- derived cell showed a positive correlation with an r of 0.65. The variance of the intrinsic capacity to produce HbF may account for almost 40% (r2) of the variance of circulating fetal hemoglobin but other factors, particularly selective survival of F cells, must also contribute significantly. Despite virtually normal HbF levels in sickle trait parents of these Saudi patients, mean fetal hemoglobin production per BFU-E-derived erythroblast in these individuals was elevated to 3.42 +/- 1.79 pg/cell or 16.1 +/- 6.4% fetal hemoglobin, and the magnitude of fetal hemoglobin production found in parents correlated with that of the patients. These data indicate that the high fetal hemoglobin in Saudi sickle cell disease is genetically determined but expressed only during accelerated erythropoiesis. Further evidence of such genetic determination was provided by analysis of DNA polymorphisms within the beta-globin gene cluster on chromosome 11. This revealed a distinctive 5′ globin haplotype (+ + - + +) on at least one chromosome 11 in all high F SS and AS tested. The precise relationship of this haplotype to HbF production in this population remains to be defined.

CELLULAR REGULATION OF FETAL HEMOGLOBIN PRODUCTION

1980 ◽  
Vol 344 (1 Fourth Cooley) ◽  
pp. 206-218 ◽  
Author(s):  
Thalia Papayannopoulou ◽  
George Stamatoyannopoulos
Keyword(s):  
Fetal Hemoglobin ◽  
Cellular Regulation ◽  
Hemoglobin Production

F Reticulocytes Assay: A Method to Evaluate Fetal Hemoglobin Production

Hemoglobin ◽  
1998 ◽  
Vol 22 (5-6) ◽  
pp. 419-425 ◽  
Author(s):  
M. Maier-Redelsperger ◽  
J. Elion ◽  
R. Girot
Keyword(s):  
Fetal Hemoglobin ◽  
Hemoglobin Production

scholarly journals Induction of fetal hemoglobin synthesis by CRISPR/Cas9-mediated editing of the human β-globin locus

Blood ◽  
2018 ◽  
Vol 131 (17) ◽  
pp. 1960-1973 ◽  
Author(s):  
Chiara Antoniani ◽  
Vasco Meneghini ◽  
Annalisa Lattanzi ◽  
Tristan Felix ◽  
Oriana Romano ◽  
...  
Keyword(s):  
Fetal Hemoglobin ◽  
Cell Phenotype ◽  
Hemoglobin Synthesis ◽  
Key Points

Key Points CRISPR/Cas9-mediated disruption of the β-globin locus architecture reactivates fetal γ-globin expression in adult erythroblasts. Fetal γ-globin reactivation and sickle β-globin downregulation leads to the amelioration of the SCD cell phenotype.

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