Special AT-rich binding protein 1 (SATB1) nuclear protein, expressed predominantly in T cells, regulates genes through targeting chromatin remodeling during T-cell maturation. Here we show SATB1 family protein induction during early human adult erythroid progenitor cell differentiation concomitant with epsilon-globin expression. Erythroid differentiation of human erythroleukemia K562 cells by h...

Peripheral blood blasts from a patient with acute megakaryoblastic leukemia were placed into liquid cultures with recombinant growth factors. Growth, but not differentiation, was supported by interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) for the first 30 days of culture. Sustained growth occurred only with GM-CSF and gave rise to the cell line MB-02, which ha...

Abnormal epigenetic regulation of gene expression contributes significantly to a variety of human pathologies including cancer. Deletion of hypersensitive site 2 (HS2) at the human beta-globin locus control region can lead to abnormal epigenetic regulation of globin genes in transgenic mice. Here, two HS2-deleted transgenic mouse lines were used as model to demonstrate that heritable alteration...

The relationship between DNA methylation and differential expression of rabbit beta-like globin genes was studied by using restriction enzymes that cleave the sequence C-C-G-G but are differentially inhibited by the presence of 5-methylcytosine. The methylation frequency of 13 C-C-G-G sites that flank a set of four closely linked rabbit beta-like globin genes was determined. This analysis revea...

Globin chain synthesis was studied in reticulocytes and bone marrow erythroid precursors in four sickle beta-thalassaemic Greek patients. Significant globin chain imbalance was found in reticulocytes (alpha/gamma + beta A + beta S = 2.20 +/- SD 0.16) and bone marrow (alpha/gamma + beta A + beta S = 1.58 +/- SD 0.11) after two hours' incubation. There was evidence of contamination of the gamma, ...

Transcription of the HIV-1 genome yields a single primary transcript, which is alternatively spliced to >30 mRNAs. Productive infection depends on inefficient and regulated splicing and appears to proceed in a tight 5' to 3' order. To analyse whether sequential splicing is mediated by the quality of splice sites or by the position of an intron, we inserted the efficient beta-globin intron (BGI)...

As initial human gene therapy trials for beta-thalassemia are contemplated, 2 critical questions important to trial design and planning have emerged. First, what proportion of genetically corrected hematopoietic stem cells (HSCs) will be needed to achieve a therapeutic benefit? Second, what level of expression of a transferred globin gene will be required to improve beta-thalassemic erythropoie...

The delineation of the thalassemia syndromes started in the late 1950s with the distinction of alpha and beta thalassemias and the initial studies that pointed out to the considerable genetic heterogeneity of these disorders. Molecular investigations, however, had to wait for the development of recombinant DNA and molecular cloning techniques in the 1970s. The thalassemias were the first human ...

The beta-globin locus control region (LCR) is contained on a 20 kb DNA fragment and is characterized by the presence of five DNaseI hypersensitive sites in erythroid cells, termed 5'HS1-5. A fully active 6.5 kb version of the LCR, called the muLCR, has been described. Expression of the beta-like globin genes is absolutely dependent on the presence of the LCR. The developmental expression patter...