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G. Hoppe, M.E. Rayborn, J. Sears; Expression of Chromatin Protein HMGB1 in Photoreceptors Is Under Circadian Regulation . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2844.
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HMGB1 belongs to a family of structure–specific DNA binding proteins with DNA chaperone–like properties that mediate a wide range of nuclear processes including regulation of transcription, DNA repair, genome stability, and stress response. We analyzed the circadian expression of HMGB1 to elucidate retinal distribution and expression mechanisms of this major non–histone nuclear protein.
Long Evans rats were entrained to cyclic light, placed in the dark for an additional 36 hrs, and eyes were collected and dissected under dim red light. Frozen sections of rat and human posterior poles were subjected to immunohistochemistry for HMGB1 and histones. Subcellular fractionation was performed using sucrose density gradient ultracentrifugation. Levels of HMGB1 mRNA were analyzed by ribonuclease protection assay.
A diurnal oscillation of HMGB1 at the protein level occurs in retinal photoreceptor cells and to lesser extent in bipolar neurons. Expression of HMGB1 was least at night at Zeitgeber time (ZT) 18 and maximal in the middle of the lights–on period (ZT6). Regulation of HMGB1 expression in photoreceptor cells was post–transcriptional, since low amplitude of diurnal mRNA changes did not mach profound fluctuations of HMGB1 protein. Within photoreceptor nuclei, HMGB1 co–localized with acetylated histone H3, a marker of euchromatin. Outside the nucleus, a distinct smaller–sized isoform of HMGB1 was also present in photoreceptor inner segments and appeared to be bound to a membrane fraction with characteristics of endoplasmic reticulum membranes. Since rhythmic expression of HMGB1 protein in photoreceptors continued in complete darkness, it is likely to be under control of a circadian clock.
The rhythmic expression of HMGB1 protein may underlie the circadian change in chromatin remodeling in addition histone acetylation.
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