Long non-coding RNA slincRAD functions in methylation regulation during the early stage of mouse adipogenesis

Adipocyte differentiation is a coordinated cellular process, which involves a series of dynamic molecular events. Up-regulation of long noncoding RNA <i>slincRAD</i> expression was found to occur in the early differentiation stages of 3T3-L1 cell, prior to the regulation of major transcription factors. By interacting with DNMT1 in S phase, <i>slincRAD</i> guides this essentially epigenetic factor to mediate promoter methylation of a batch of cell cycle-related genes, including cyclin-dependent kinase inhibitor <i>p21</i>. The regulation promotes the growth-arrested cells to re-enter into cell cycle under hormone induction and thereby advances the process of differentiation to clonal expansion stage. The abolishment of the interaction between <i>slincRAD</i> and DNMT1 by <i>slincRAD</i> knockdown results in a defective epigenetic regulation and finally compromised adipogenesis. Collectively, our study characterizes the epigenetic regulation of lncRNA involved in the early stage of adipogenesis.

脂肪细胞分化是一类高度协同的细胞进程，涵盖一系列动态分子事件。研究发现，长链非编码RNA（long noncoding RNA，lncRNA）<i>slincRAD</i>的表达上调发生于3T3-L1细胞分化的早期阶段，早于核心转录因子的调控过程。<i>slincRAD</i>可在S期与DNA甲基转移酶1（DNMT1）相互作用，引导这一关键表观遗传因子介导一批细胞周期相关基因的启动子甲基化，其中包括细胞周期蛋白依赖性激酶抑制剂<i>p21</i>。该调控作用可促使生长阻滞的细胞在激素诱导下重新进入细胞周期，进而推动分化进程进入克隆扩增阶段。通过<i>slincRAD</i>敲低阻断其与DNMT1的相互作用，会导致表观遗传调控缺陷，最终削弱脂肪生成过程。综上，本研究阐明了长链非编码RNA介导的表观遗传调控在脂肪生成早期阶段的功能特征。