The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Induction of γ-Globin by Histone Deacetylase Inhibitors
Abstract
The short-chain fatty acid butyrate has been shown to elevate fetal hemoglobin (HbF ) by inducing expression of the γ-globin gene. Regulation of gene expression by butyrate is thought to proceed via inhibition of the enzyme histone deacetylase, leading to elevated levels of core histone acetylation which affect chromatin structure and transcription rates. To determine whether changes in histone acetylation are critical for the regulation of the γ-globin gene, we tested three potent and specific inhibitors of histone deacetylase, the cyclic tetrapeptides trapoxin and Helminthsporium carbonum toxin (HC toxin), and the antifungal antibiotic trichostatin A for their ability to induce fetal hemoglobin expression in erythroid cells. These compounds induced fetal hemoglobin in both primary erythroid cell cultures and human erythroleukemia (K562) cells. A butyrate-responsive element spanning the duplicated CCAAT box region of the γ-globin promoter has been identified in transient transfection assays using a reporter construct in K562 cells, and we show that the same promoter region is required for response to trapoxin and trichostatin. Mutational analysis of the γ-globin promoter indicates that the distal CCAAT box and 3′ flanking sequence (CCAATAGCC) is critical for activation by butyrate, trapoxin, and trichostatin, whereas the proximal element (CCAATAGTC) plays a less important role. These results show that inhibition of histone deacetylase can lead to transcriptional activation of γ-globin promoter reporter gene constructs through proximal promoter elements, and suggest that butyrate induces γ-globin expression via such changes in histone acetylation.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The aberrant recruitment of HDAC1 has been linked to various types of leukemia, and an HDACi has shown clinical and preclinical promise as a result of its ability to induce leukemic cell differentiation and death (64–68).”
From Histone deacetylase 1 activates PU.1 gene transcription through regulating TAF9 deacetylation and transcription factor IID assembly (2017) · cites this paper as [67]
In the citing paper
“The aberrant recruitment of HDAC1 has been linked to various types of leukemia, and an HDACi has shown clinical and preclinical promise as a result of its ability to induce leukemic cell differentiation and death (64–68).”
From Histone deacetylase 1 activates PU.1 gene transcription through regulating TAF9 deacetylation and transcription factor IID assembly (2017) · cites this paper as [67]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
A Mammalian Histone Deacetylase Related to the Yeast Transcriptional Regulator Rpd3p
Taunton, J., Hassig, C. A., & Schreiber, S. L. (1996) · Science · doi:10.1126/science.272.5260.408 · Cited by 1,829
Brosch, G., Ransom, R., Lechner, T., Walton, J. D., & Loidl, P. (1995) · The Plant Cell · doi:10.1105/tpc.7.11.1941 · Cited by 204
Fibach, E., Burke, L., Schechter, A., Noguchi, C., & Rodgers, G. (1993) · Blood · doi:10.1182/blood.v81.6.1630.1630 · Cited by 102
Self-citation
Research works printed but not linked: 32
- Perrine, 1988, Butyrate infusions in the ovine fetus delay the biologic clock for globin gene switching., Proc Natl Acad Sci USA, 85, 8540, 10.1073/pnas.85.22.8540 · DOI
- Perrine, 1993, A short-term trial of butyrate to stimulate fetal-globin-gene expression in the beta-globin disorders., N Engl J Med, 328, 81, 10.1056/NEJM199301143280202 · DOI
- Turner, 1991, Histone acetylation and control of gene expression., J Cell Sci, 99, 13, 10.1242/jcs.99.1.13 · DOI
- Candido, 1978, Sodium butyrate inhibits histone deacetylation in cultured cells., Cell, 14, 105, 10.1016/0092-8674(78)90305-7 · DOI · Paper page
- Yoshida, 1995, Trichostatin A and trapoxin: Novel chemical probes for the role of histone acetylation in chromatin structure and function., BioEssays, 17, 423, 10.1002/bies.950170510 · DOI
- Kijima, 1993, Trapoxin, an antitumor cyclic tetrapeptide, is an irreversible inhibitor of mammalian histone deacetylase., J Biol Chem, 268, 22429, 10.1016/S0021-9258(18)41547-5 · DOI
- Yoshida, 1990, Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A., J Biol Chem, 265, 17174, 10.1016/S0021-9258(17)44885-X · DOI
- Fibach, 1989, Proliferation and maturation of human erythroid progenitors in liquid culture., Blood, 73, 100, 10.1182/blood.V73.1.100.100 · DOI
- Fibach, 1993, Enhanced fetal hemoglobin production by phenylacetate and 4-phenylbutyrate in erythroid precursors serived from normal donors and patients with sickle cell anemia and β-thalassemia., Blood, 82, 2203, 10.1182/blood.V82.7.2203.2203 · DOI
- Rutherford, 1981, Embryonic erythroid differentiation in the human leukemic cell line K562., Proc Natl Acad Sci USA, 78, 348, 10.1073/pnas.78.1.348 · DOI
- Safaya, 1994, Augmentation of γ-globin gene promoter activity by carboxylic acids and components of the human β-globin locus control region., Blood, 84, 3929, 10.1182/blood.V84.11.3929.bloodjournal84113929 · DOI
- Neumann, 1987, A novel rapid assay for chloramphenicol acetyltransferase gene expression., Biotechniques, 5, 444
- Cioe, 1981, Differential expression of the globin genes in human leukemia K562(S) cells induced to differentiate by hemin or butyric acid., Cancer Res, 41, 237
- Pace, 1996, In vivo search for butyrate responsive sequences using transgenic mice carrying Aγ gene promoter mutants., Blood, 88, 1079, 10.1182/blood.V88.3.1079.1079 · DOI
- Ulrich, 1990, Function of normal and mutated γ-globin promoters in electroporated K562 erythroleukemia cells., Blood, 75, 990, 10.1182/blood.V75.4.990.990 · DOI
- McDonagh, 1991, The upstream region of the human γ-globin gene promoter: Identification and functional analysis of nuclear protein binding sites., J Biol Chem, 266, 11965, 10.1016/S0021-9258(18)99051-4 · DOI
- Perez-Stable, 1990, Roles of fetal Gγ-globin promoter elements and the adult β-globin 3′ enhancer in the stage-specific expression of globin genes., Mol Cell Biol, 10, 1116, 10.1128/MCB.10.3.1116 · DOI
- Katsube, 1995, A role for the distal CCAAT box of the γ-globin gene in Hb switching., J Biochem, 117, 68, 10.1093/oxfordjournals.jbchem.a124723 · DOI
- Lavelle, 1993, Fetal hemoglobin reactivation in baboon and man: A short perspective., Am J Hematol, 42, 91, 10.1002/ajh.2830420118 · DOI
- MCDonagh, 1992, Hydroxyurea-induced HbF production in anemic primates: Augmentation by erythropoietin, hematopoietic growth factors, and sodium butyrate., Exp Hematol, 20, 1156
- Constantoulakis, 1989, On the induction of fetal hemoglobin by butyrates: In vivo and in vitro studies with sodium butyrate and comparison of comiination treatments with 5-AzaC and AraC., Blood, 74, 1963, 10.1182/blood.V74.6.1963.1963 · DOI
- Sekhara, 1994, Genomic footprinting and sequencing of the human β-globin locus., J Biol Chem, 269, 8287, 10.1016/S0021-9258(17)37191-0 · DOI
- Fischer, 1993, Cooperation of GATA-1 and Sp1 can result in synergistic transcriptional activation or interference., J Biol Chem, 268, 23915, 10.1016/S0021-9258(20)80472-4 · DOI
- Vettese-Dady, 1996, Acetylation of histone H4 plays a primary role in enhancing transcription factor binding to nucleosomal DNA in vitro., EMBO J, 15, 2508, 10.1002/j.1460-2075.1996.tb00608.x · DOI
- Neufeld, 1992, Human CCAAT displacement protein in homologous to the Drosophila homeoprotein, cut., Nat Genet, 1, 50, 10.1038/ng0492-50 · DOI
- Superti-Furga, 1988, The −117 mutation in Greek HPHF affects the biding of three nuclear factors to the CCAAT region of the γ-globin gene., EMBO J, 7, 3099, 10.1002/j.1460-2075.1988.tb03176.x · DOI
- Ronchi, 1995, Differential binding of the NFE3 and CP1/NFY transcription factors to the human γ- and ε-globin CCAAT boxes., J Biol Chem, 270, 21934, 10.1074/jbc.270.37.21934 · DOI
- Stamatoyannopoulos, 1993, Developmental regulation of human γ globin genes in transgenic mice., Mol Cell Biol, 13, 7636, 10.1128/MCB.13.12.7636 · DOI
- Pennisi, 1997, Opening the way to gene activity., Science, 275, 155, 10.1126/science.275.5297.155 · DOI
- Lopez-Rodas, 1991, Histone acetylation in Zea mays I: Activities of histone acetyltransferases and histone deacetylases., J Biol Chem, 266, 18745, 10.1016/S0021-9258(18)55126-7 · DOI
- Calabresse, 1993, Butyric acid and its monosaccharide ester induce apoptosis in the HL-60 cell line., Biochem Biophys Res Commun, 195, 31, 10.1006/bbrc.1993.2005 · DOI
- Hague, 1993, Sodium butyrate induces apoptosis in human colonic tumour cell lines in a p53-independent pathway: Implications for the possible role of dietary fibre in the prevention of large-bowel cancer., Int J Cancer, 55, 498, 10.1002/ijc.2910550329 · DOI
Cited by
Sorted by citations
Zhang, W., & Bieker, J. J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.17.9855 · Cited by 342
Chiurazzi, P., Grazia Pomponi, M., Pietrobono, R., Bakker, C. E., Neri, G., & Oostra, B. A. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.12.2317 · Cited by 217
Zhang, W., Kadam, S., Emerson, B. M., & Bieker, J. J. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.7.2413-2422.2001 · Cited by 182
Kosugi, H., Towatari, M., Hatano, S., Kitamura, K., Kiyoi, H., Kinoshita, T., Tanimoto, M., Murate, T., Kawashima, K., Saito, H., et al. (1999) · Leukemia · doi:10.1038/sj.leu.2401508 · Cited by 150
Jian, W., Yan, B., Huang, S., & Qiu, Y. (2017) · The FASEB Journal · doi:10.1096/fj.201700022r · Cited by 23
Metadata
- Authors
- McCaffrey, P. G., Newsome, D. A., Fibach, E., Yoshida, M., & Su, M. S.-S.
- Affiliations
- From the Molecular Biology Department, Vertex Pharmaceuticals Inc, Cambridge, MA; the Department of Hematology, Hadassah University Hospital, Jerusalem, Israel; Laboratory of Chemical Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD; the Department of Biotechnology, University of Tokyo, Tokyo, Japan.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 1997-09-01
- Volume
- 90
- Issue
- 5
- Pages
- 2075-2083
- ISSN
- 1528-0020
- 0006-4971
- Cited by
- 118
- References
- 3
- Language
- en
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Induction of γ-Globin by Histone Deacetylase Inhibitors. https://app.cochat.ai/papers/10.1182/blood.v90.5.2075
- The paper
- McCaffrey, P. G., Newsome, D. A., Fibach, E., Yoshida, M., & Su, M. S.-S. (1997). Induction of γ-Globin by Histone Deacetylase Inhibitors. Blood. https://doi.org/10.1182/blood.v90.5.2075
