Wu Su, Hu Yueh-Chiang, Liu Huifei, Shi Yang
Department of Pathology, Harvard Medical School, New Research Building 854b, Boston, MA 02115, USA.
Mol Cell Biol. 2009 Dec;29(23):6245-56. doi: 10.1128/MCB.00679-09. Epub 2009 Sep 28.
The progression of spermatogenesis involves global changes in chromatin structure and conformation. However, our understanding of the regulation of chromatin changes in germ cells remains limited. Here we describe both in vivo RNA interference and genetic mouse knockout studies that identify a critical role for Yin Yang 1 (YY1) in mammalian spermatogenesis. In the YY1-deficient spermatocytes, we find a significant decrease in the global level of the heterochromatin markers (H3K9me3 and HP1-gamma) and a concomitant increase in the double-strand break (DSB) signals on chromosomes (gamma-H2AX, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling, and Rad51) at the leptotene/zygotene stages of spermatocytes. These findings support a link between chromatin modifications and meiotic DSB formation, as has been seen in other model organisms. We propose that a depletion of YY1 may alter the structural integrity of heterochromatin, rendering it more accessible to the DSB machinery. In addition, YY1-deficient spermatocytes show univalent formation, increased aneuploidy, and pachytene cell death, which are likely due to defects in DNA repair. Taken together, this study identifies an important role for YY1 in mouse meiosis and provides new insight into mechanisms that regulate mammalian spermatogenesis.
精子发生的过程涉及染色质结构和构象的整体变化。然而，我们对生殖细胞中染色质变化调控的理解仍然有限。在此，我们描述了体内RNA干扰和基因敲除小鼠研究，这些研究确定了阴阳1（YY1）在哺乳动物精子发生中的关键作用。在YY1缺陷的精母细胞中，我们发现异染色质标记物（H3K9me3和HP1-γ）的整体水平显著降低，同时在精母细胞细线期/偶线期染色体上的双链断裂（DSB）信号（γ-H2AX、末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记和Rad51）增加。这些发现支持了染色质修饰与减数分裂DSB形成之间的联系，这在其他模式生物中也有发现。我们提出，YY1的缺失可能会改变异染色质的结构完整性，使其更容易被DSB机制作用。此外，YY1缺陷的精母细胞表现出单价体形成、非整倍体增加和粗线期细胞死亡，这可能是由于DNA修复缺陷所致。综上所述，本研究确定了YY1在小鼠减数分裂中的重要作用，并为调控哺乳动物精子发生的机制提供了新的见解。
