Butyric acid modulates developmental globin gene switching in man and sheep

Advances in Experimental Medicine and Biology
S P PerrineY W Kan

Abstract

The developmental switch from production of fetal (gamma) to adult (beta) globin occurs on a normally set biologic clock which proceeds even if the adult (beta) globin genes are defective. Preventing or reversing the globin gene switch would be beneficial for subjects with abnormal beta globin genes. We have now identified a class of agents which, when present in elevated plasma concentrations during gestation, appears to inhibit the gamma beta globin gene switch in developing humans. Further investigation has shown that butyric acid and related compounds can increase gamma globin and decrease beta globin expression in erythroid cells cultured from subjects with diseases of abnormal beta globin. Butyrate compounds were therefore infused in an in vivo fetal animal model, and the globin switch was inhibited in most and reversed in some fetal lambs. These data suggest that inhibiting expression of abnormal beta globin genes may be possible in future generations. Histone modification may be a mechanism of action involved. The developmental switch from production of gamma globin to beta globin results in significant morbidity when the beta globin genes are defective. The globin switch has therefore been extensively studied, appearin...Continue Reading

Citations

Aug 16, 2001·Proceedings of the National Academy of Sciences of the United States of America·J G ChangH Li
Jun 4, 2002·Current Opinion in Hematology·Ari Melnick, Jonathan D Licht
Mar 1, 2016·Iranian Journal of Biotechnology·Mahmoud Shekari KhanianiSima Mansoori Derakhshan
Apr 12, 2006·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Betty S Pace, Sima Zein
Jul 23, 2021·Experimental Biology and Medicine·Athena Starlard-DavenportBetty S Pace

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