SUMMARYDuring meiosis, specific histone modifications at pericentric heterochromatin (PCH), especially histone H3 tri-and dimethylation at lysine 9 (H3K9me3 and H3K9me2, respectively), are required for proper chromosome interactions. However, the molecular mechanism by which H3K9 methylation mediates the synapsis is not yet understood. We have generated a Cbx3-deficient mouse line and performed comparative analysis on Suv39h1/h2-, G9a-and Cbx3-deficient spermatocytes. This study revealed that H3K9me2 at PCH depended on Suv39h1/h2-mediated H3K9me3 and its recognition by the Cbx3 gene product HP1. We further found that centromere clustering and synapsis were commonly affected in G9a-and Cbx3-deficient spermatocytes. These genetic observations suggest that HP1/G9a-dependent PCH-mediated centromere clustering is an axis for proper chromosome interactions during meiotic prophase. We propose that the role of the HP1/G9a axis is to retain centromeric regions of unpaired homologous chromosomes in close alignment and facilitate progression of their pairing in early meiotic prophase. This study also reveals considerable plasticity in the interplay between different histone modifications and suggests that such stepwise and dynamic epigenetic modifications may play a pivotal role in meiosis.

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Abstract. Vitamin A deficiency (VAD) caused by malnutrition and certain intestinal diseases induces visual impairments, including night blindness and photoreceptor cell dysfunction as indicated by reduced a-and b-waves in an electroretinogram (ERG). The effects of VAD on the inner retinal layer cells, including amacrine and ganglion cells, remain to be elucidated. The functions of these cells are reflected in oscillatory potentials (OPs), another component of the ERG. The present study investigated inner retinal layer cell function in VAD rats by analyzing OPs. In the present study, VAD was induced by feeding Brown Norway rats a vitamin A deficient diet for 10 weeks. A reduced body weight and peri-papillary opacification indicative of papilledema without histopathological alterations were observed, which are considered early symptoms of VAD. At this stage, the ERG revealed reduced OPs as well as a-and b-waves at various intensities of light stimulation. Further analysis indicated that the ratio of the alterations in OPs was more significant than those of a-and b-waves. After 5 weeks of recovery, these changes returned to control levels. These results suggest that OPs are the most sensitive and early marker of VAD-associated visual impairment in the ERG. IntroductionRetinoids, derivatives of vitamin A (Vit A), have essential roles in visual phototransduction. In the initial step of visual phototransduction, conversion of 11-cis retinal to all-trans (AT) retinal occurs in photoreceptor cells subjected to light exposure. Vitamin A deficiency (VAD) reduces this activity and subsequent downstream reactions in photoreceptor cells. As a result, patients with VAD exhibit visual abnormalities, including abnormal dark adaptation and night blindness, which may eventually progress to a severe visual impairment (1-3). Consistent with these clinical symptoms, electroretinogram (ERG) recordings in humans with VAD show decreases in amplitudes or loss of a-and b-waves, which reflect the function of photoreceptor and bipolar cells, respectively (1,3). A previous study reported that a reduced a-wave and a partial reduction of b-wave are induced by feeding albino rats a Vit A deficient diet for 8 weeks, with disintegration of the outer segments of photoreceptor cells (4). In contrast to the established effects of VAD on the a-and b-waves in ERG and histological alterations in photoreceptors, the effects of VAD on oscillatory potentials (OPs) remain to be elucidated. OPs, which are components of the ERG, are considered to be generated by the inner retinal layer cells, including amacrine and ganglion cells (5) and the reduction of OPs is known to be associated with reduced contrast sensitivity in diabetic patients (6). VAD has also been reported to reduce contrast sensitivity (7). Therefore, although, to the best of our knowledge, there are no studies indicating that VAD directly affects the formation of OPs or the function of inner retinal layer cells, it was hypothesized that OPs in ERG recordings may be affected during a state of ...