Sodium butyrate induces histone hyperacetylation and differentiation of murine embryonal carcinoma cells.
Cells from embryonal carcinoma (EC) lines 6050AJ and PCC4.aza 1R differentiate in response to treatment with sodium butyrate as well as retinoic acid (RA) or hexamethylenebisacetamide (HMBA). Murine 6050AJ EC cells exposed to sodium butyrate possess hyperacetylated forms of histones H4 and altered forms of histones H2a and H2b, whereas histones from cells treated with other inducers appear to be unaffected. These results might indicate that the mechanism by which sodium butyrate promotes differentiation of EC cells is different from the ways in which RA and HMBA act. Differentiation-defective PCC4(RA)-1 EC cells fail to respond to RA, presumably because they possess minimal amounts of active binding protein for RA (cRABP). Sodium butyrate treatment of these cells results in only a modest level of differentiation. On the other hand, exposure to sodium butyrate plus RA leads to extensive differentiation. As is the case with 6050AJ cells, PCC4(RA)-1 cells treated with sodium butyrate also contain hyperacetylated histones. Furthermore, these cells now possess high levels of cRABP. The latter observations suggest that sodium butyrate has the ability to reactivate a silent cRABP gene in PCC4(RA)-1 cells and thereby lead to extensive differentiation via the retinoid pathway when RA is added.
D000107:Acetylation; D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D054278:Embryonal Carcinoma Stem Cells; D006017:Glycolipids / Q000032:analysis; D006657:Histones / Q000378:metabolism*; D016256:Lewis X Antigen; D051379:Mice; D014411:Neoplastic Stem Cells / Q000503:physiopathology*; D018168:Receptors, Retinoic Acid; D013234:Stem Cells / Q000503:physiopathology*; D013724:Teratoma / Q000503:physiopathology*; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology
D000951:Antigens, Neoplasm; D002087:Butyrates; D002352:Carrier Proteins; D006017:Glycolipids; D006657:Histones; D016256:Lewis X Antigen; D018168:Receptors, Retinoic Acid; D020148:Butyric Acid; D014212:Tretinoin