背景回顾：The MADS domain transcription factor AGAMOUS (AG) regulates floral meristem termination by preventing maintenance of the histone modification H3K27me3 along the KNUCKLES (KNU) coding sequence. At two days after AG binding, cell division has diluted the repressive mark H3K27me3, allowing activation of KNU transcription prior to floral meristem termination. 

提出问题：However, how many other downstream genes are temporally regulated by this intrinsic epigenetic timer and what their functions are remain unknown. 

主要发现：Here, we identify direct AG targets regulated through cell cycle–coupled H3K27me3 dilution in Arabidopsis thaliana. 

结果1-AG靶基因：Expression of the targets KNU, AT HOOK MOTIF NUCLEAR LOCALIZED PROTEIN18 (AHL18), and PLATZ10 occurred later in plants with longer H3K27me3-marked regions. 

结果2-KNU时序调控：We established a mathematical model to predict timing of gene expression and manipulated temporal gene expression using the H3K27me3-marked del region from the KNU coding sequence. Increasing the number of del copies delayed and reduced KNU expression in a Polycomb Repressive Complex 2– and cell cycle–dependent manner. 

结果3-AHL18时序调控：Furthermore, AHL18 was specifically expressed in stamens and caused developmental defects when mis-expressed. Finally, AHL18 bound to genes important for stamen growth. 

结论：Our results suggest that AG controls the timing of expression of various target genes via cell cycle–coupled dilution of H3K27me3 for proper floral meristem termination and stamen development.

MADS-box转录因子AG通过防止组蛋白修饰H3K27me3在KNU基因编码区上的维持，从而调控花分生组织终止。在AG结合后的两天，细胞分裂会稀释掉抑制性标记H3K27me3，使得KNU转录在花分生组织终止之前得以被激活。但是，很多其它下游的基因是如何被这种植物体内表观“计时器”所时序调节的，以及这种调控的功能还不清楚。本文中，作者鉴定到了由AG通过细胞周期耦联的H3K27me3稀释来调控的直接靶基因。靶标KNU、AHL18和PLATZ10的H3K27me3修饰区更长，在植株中的表达会更晚。作者建立了一个数学模型，预测基因的表达，并且通过KNU编码序列中H3K27me3标记的del区来操纵基因的表达时间。del拷贝数的增加会导致KNU表达滞后且降低，并且这一过程依赖于PRC2和细胞周期。此外，AHL18特异性地在雄蕊中表达，其表达错误会导致雄蕊的发育缺陷。最终，AHL18会结合到雄蕊生长关键基因上。本文的结果显示，AG通过细胞周期耦联的H3K27me3稀释，调控其靶标基因的表达时机，从而作用于正确的花分生组织终止和雄蕊发育。