α-Amino butyric acid cannot reactivate the silenced γ gene of the β locus YAC transgenic mouse

Betty Sue Pace, Qiliang Li, Kenneth Peterson, George Stamatoyannopoulos

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Butyric acid, a naturally occurring fatty acid, has been shown to increase fetal hemoglobin in BFUe cultures, in primates, and in patients with β chain hemoglobinopathies. The precise mechanism of γ gene induction by butyrate is unknown. Butyrate may induce fetal hemoglobin production in vivo by reactivation of silenced γ globin genes, by inhibiting the silencing of γ genes, or by both mechanisms. We examined the effects of butyrate on γ gene expression in transgenic mice carrying three types of constructs: μLCR(A)γ mice, which continue to express the γ gene in the adult stage of development at a level of one-third to one-fifth of the expression in the fetus; μLCR(A)γχβΔβ mice, which display correct developmental regulation of γ and β human globin genes and have low level γ globin expression in the adult; and β locus YAC mice, which display correct developmental regulation of ε, γ, and β globin genes and have a totally silenced γ gene in the adult stage. Animals were treated with a continuous infusion of α-amino butyric acid (α-ABA) for 7 days. In μLCR(A)γ mice α-ABA produced up to a 43-fold induction of γ and 9-fold induction of mouse α globin genes. In contrast, butyrate did not induce γ globin expression in the β locus YAC mice. However, the γ globin genes of β locus YAC mice were activated after administration of 5-azacytidine (5-azaC), and the level of γ globin expression was further increased by administration of α-ABA. These results suggest that butyrate cannot reactivate a totally silenced γ gene and that induction of fetal hemoglobin by this compound may require the presence of preactivated γ globin genes.

Original languageEnglish (US)
Pages (from-to)4344-4353
Number of pages10
JournalBlood
Volume84
Issue number12
StatePublished - Dec 15 1994
Externally publishedYes

Fingerprint

Butyric Acid
Globins
Transgenic Mice
Genes
Butyrates
Fetal Hemoglobin
Azacitidine
Hemoglobinopathies
Gene Silencing
Primates
Gene expression
Fetus
Fatty Acids
Animals
Gene Expression

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Pace, B. S., Li, Q., Peterson, K., & Stamatoyannopoulos, G. (1994). α-Amino butyric acid cannot reactivate the silenced γ gene of the β locus YAC transgenic mouse. Blood, 84(12), 4344-4353.

α-Amino butyric acid cannot reactivate the silenced γ gene of the β locus YAC transgenic mouse. / Pace, Betty Sue; Li, Qiliang; Peterson, Kenneth; Stamatoyannopoulos, George.

In: Blood, Vol. 84, No. 12, 15.12.1994, p. 4344-4353.

Research output: Contribution to journalArticle

Pace, BS, Li, Q, Peterson, K & Stamatoyannopoulos, G 1994, 'α-Amino butyric acid cannot reactivate the silenced γ gene of the β locus YAC transgenic mouse', Blood, vol. 84, no. 12, pp. 4344-4353.
Pace BS, Li Q, Peterson K, Stamatoyannopoulos G. α-Amino butyric acid cannot reactivate the silenced γ gene of the β locus YAC transgenic mouse. Blood. 1994 Dec 15;84(12):4344-4353.
Pace, Betty Sue ; Li, Qiliang ; Peterson, Kenneth ; Stamatoyannopoulos, George. / α-Amino butyric acid cannot reactivate the silenced γ gene of the β locus YAC transgenic mouse. In: Blood. 1994 ; Vol. 84, No. 12. pp. 4344-4353.
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