Changes in gene expression of histone modification enzymes in rat granulosa cells undergoing luteinization during ovulation.
Changes in gene expression of histone modification enzymes in rat granulosa cells undergoing luteinization during ovulation.
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DOI：
10.1186/s13048-016-0225-z
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发表时间：
2016-03-15
影响因子：
4
通讯作者：
Sugino N
中科院分区：
文献类型：
--
作者：
Maekawa R;Lee L;Okada M;Asada H;Shinagawa M;Tamura I;Sato S;Tamura H;Sugino N
排卵LH峰迅速改变类固醇生成相关基因的表达，如类固醇生成急性调节蛋白（星星）在颗粒细胞（GC）进行黄体化。我们最近报道，组蛋白修饰有助于这些变化。组蛋白修饰受多种组蛋白修饰酶的调控。本研究探讨了促排卵后黄体化大鼠GC中组蛋白修饰酶基因表达的变化。细胞外调节激酶（ERK）-1/2是由排卵性LH峰刺激的细胞内信号通路中的介导者，并且调节GC中许多基因的表达。我们进一步研究了ERK-1/2是否参与了GCs发生黄素化时星星启动子区组蛋白修饰的调节。在注射人绒毛膜促性腺激素（CG）之前（0 h）和之后（h），从接受马绒毛膜促性腺激素（CG）处理的大鼠中获得GC。使用PCR阵列测量了84个调节组蛋白修饰或DNA甲基化的基因的表达。5个基因（HDAC 4，HDAC 10，EZH 2，SETDB 2和CIITA）被鉴定为组蛋白乙酰化或组蛋白甲基化相关基因，并在hCG注射后显著改变。没有一个基因与DNA甲基化有关。hCG注射后4或12 h，EZH 2、SETDB 2、HDAC 4和HDAC 10的mRNA水平降低，CIITA mRNA水平升高。将eCG注射后分离的GC与hCG孵育4小时以诱导黄体化。星星mRNA水平显着增加hCG伴随着星星启动子区的H3 K4 me 3的增加。ERK抑制剂可抑制星星mRNA的表达，并使H3 K4 me 3显著降低。这些结果表明，hCG通过ERK-1/2介导的信号传导增加星星基因表达，这也与启动子区的组蛋白修饰有关。组蛋白修饰酶基因表达的变化在促排卵后经历黄体化的GC中。这种变化可能在调节黄体化早期各种基因的表达中起重要作用，这可能对随后的黄体形成至关重要。
The ovulatory LH surge rapidly alters the expression of steroidogenesis-related genes such as steroidogenic acute regulatory protein (StAR) in granulosa cells (GCs) undergoing luteinization. We recently reported that histone modifications contribute to these changes. Histone modifications are regulated by a variety of histone modification enzymes. This study investigated the changes in gene expression of histone modification enzymes in rat GCs undergoing luteinization after the induction of ovulation. The extracellular regulated kinase (ERK)-1/2 is a mediator in the intracellular signaling pathway stimulated by the ovulatory LH surge and regulates the expression of a number of genes in GCs. We further investigated whether ERK-1/2 is involved in the regulation of the histone modification at the StAR promoter region in GCs undergoing luteinization. GCs were obtained from rats treated with equine chorionic gonadotropin (CG) before (0 h) and after human (h) CG injection. The expressions of 84 genes regulating histone modifications or DNA methylation were measured using a PCR array. Five genes (HDAC4, HDAC10, EZH2, SETDB2, and CIITA) were identified as histone acetylation- or histone methylation-related genes, and were significantly altered after hCG injection. None of the genes were related to DNA methylation. mRNA levels of EZH2, SETDB2, HDAC4, and HDAC10 decreased and CIITA mRNA levels increased 4 or 12 h after hCG injection. GCs isolated after eCG injection were incubated with hCG for 4 h to induce luteinization. StAR mRNA levels were significantly increased by hCG accompanied by the increase in H3K4me3 of the StAR promoter region. StAR mRNA expression was inhibited by the ERK inhibitor with the significant decrease of H3K4me3. These results suggest that hCG increases StAR gene expression through the ERK-1/2-mediated signaling which is also associated with histone modification of the promoter region. Gene expressions of histone modification enzymes change in GCs undergoing luteinization after ovulation induction. This change may play important roles in regulating the expression of various genes during the early stage of luteinization, which may be critical for the subsequent corpus luteum formation.