Histone H3 Phosphorylation in the Rat Pineal Gland: Adrenergic Regulation and Diurnal Variation

• Published in: Endocrinology (Philadelphia) 2007-04, Vol.148 (4), p.1465-1472
• Main Authors: Chik, C. L, Arnason, T. G, Dukewich, W. G, Price, D. M, Ranger, A, Ho, A. K
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cells, Cultured; Circadian Rhythm; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases - metabolism; Dephosphorylation; Diurnal variations; Endocrine system; Fundamental and applied biological sciences. Psychology; Histone H3; Histones; Histones - metabolism; Kinases; Light; Male; Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors; Norepinephrine; Norepinephrine - pharmacology; Okadaic acid; Phosphoric Monoester Hydrolases - antagonists & inhibitors; Phosphorylation; Pineal gland; Pineal Gland - drug effects; Pineal Gland - metabolism; Prazosin; Propranolol; Protein kinase A; Protein kinase A inhibitors; Protein-serine/threonine phosphatase; Proteins; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, beta - metabolism; Threonine phosphatase; Transcription activation; Vertebrates: endocrinology
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2006-1454

In this study, we investigated phosphorylation of Ser10 in histone H3 by norepinephrine (NE) in the rat pineal gland. In whole-animal studies, we demonstrated a marked increase in histone H3 phosphorylation in the rat pineal gland during the first half of the dark period. Exposure to light during this period caused a rapid decline in histone H3 phosphorylation with an estimated t1/2 of less than 15 min, indicating a high level of dephosphorylation activity. Corresponding studies in cultured pineal cells revealed that treatment with NE produced an increase in histone H3 phosphorylation that peaked between 2 and 3 h and declined rapidly by 4 h. The NE-induced histone H3 phosphorylation was blocked by cotreatment with propranolol or KT5720, a protein kinase A inhibitor, but not by prazosin or other kinase inhibitors. Moreover, only treatment with dibutyryl cAMP but not other kinase activators mimicked the effect of NE on histone H3 phosphorylation. The NE-stimulated H3 phosphorylation was markedly increased by cotreatment with a serine/threonine phosphatase inhibitor, tautomycin or okadaic acid, supporting a high level of ongoing histone H3 dephosphorylation activity. Together, our results indicate that histone H3 phosphorylation is a naturally occurring event at night in the rat pineal gland that is driven almost exclusively by a NE→β-adrenergic→cAMP/protein kinase A signaling mechanism. This transient histone H3 phosphorylation probably reflects the nocturnal activation of multiple adrenergic-regulated genes in the rat pineal gland.