Cho Sunwha, Park Jung Sun, Kwon Sujin, Kang Yong-Kook
Development and Differentiation Research Center, KRIBB, 111 Gwahangno, Yuseong-gu, Daejeon 305-806, South Korea.
Gene Expr Patterns. 2012 May-Jun;12(5-6):213-8. doi: 10.1016/j.gep.2012.03.005. Epub 2012 Apr 5.
Setdb1/Eset, a histone lysine methyltransferase, is recruited by various transcription factors to modify local chromatin. The observation that Setdb1-null blastocysts fail to produce epiblast-lineage cells suggests a role for Setdb1 in generating mouse embryonic stem cells (mESCs). When examined in mouse zygotes, Setdb1 proteins appeared as dots at perinucleolar rims of pronuclei, with the dot-shaped signals more prominent in male pronuclei. Setdb1 signals were observed diffusely in the nucleus from the two-cell stage onward and, by the blastocyst, took a punctate form, away from nucleolus. Such varying expression patterns suggest its involvement in diverse biological processes at preimplantation stage. Setdb1 appeared in Oct4-positive cells of inner-cell-mass origin but not in trophectoderm-lineage cells in blastocyst outgrowths. Setdb1 co-immunoprecipitated with Oct4 in mESCs, and Setdb1 expression was markedly reduced upon retinoic acid-induced differentiation. These observations suggest that Setdb1 has an important role in maintaining the self-renewal of mESCs through collaboration with Oct4.
Setdb1/Eset是一种组蛋白赖氨酸甲基转移酶，可被多种转录因子招募以修饰局部染色质。Setdb1基因敲除的囊胚无法产生上胚层谱系细胞，这一观察结果表明Setdb1在小鼠胚胎干细胞（mESC）的生成中发挥作用。在小鼠受精卵中检测时，Setdb1蛋白在原核的核仁周围边缘呈现为点状，且点状信号在雄原核中更为明显。从二细胞阶段开始，Setdb1信号在细胞核中呈弥散分布，到囊胚期时，其呈现为点状，远离核仁。这种不同的表达模式表明它在植入前阶段参与了多种生物学过程。Setdb1出现在内细胞团来源的Oct4阳性细胞中，但在囊胚外植体的滋养外胚层谱系细胞中未出现。在mESC中，Setdb1与Oct4进行了共免疫沉淀，并且在视黄酸诱导分化后，Setdb1的表达明显降低。这些观察结果表明，Setdb1通过与Oct4协作，在维持mESC的自我更新中发挥重要作用。
