However, accumulating evidence also revealed potential functional differences between the two em /em -arrestins subtypes as well as their receptor specificity. role of em /em -arrestin1 in CML progression, as well as being a key regulator of H4 acetylation modification. Both em /em -arrestin1 and em /em -arrestin2 were previously known as cytosolic signalling regulatory and scaffold proteins. The activation of GPCR recruits both em /em -arrestin1 and em /em -arrestin2 to the cell membrane and interactions of the phosphorylated GPCR and em /em -arrestins induce receptor endocytosis and signal inhibition. However, accumulating evidence also revealed potential functional differences between the two em /em -arrestins subtypes as well as their receptor specificity. For example, previous studies exhibited that em /em -arrestin1 or em /em -arrestin2 has a vital role in epigenetic regulation of genes (Lefkowitz and Whalen, 2004; Kang em et al /em , 2005; Kovacs em et al /em , 2009; Yue em et al /em , 2009). Although em /em -arrestin2 has been discovered to mediate the initiation and progression of CML (Fereshteh em et al /em , 2012), the crucial role of em /em -arrestin1 is still lacking. Our results of em /em -arrestin1 in CML, together with previous study of em /em -arrestin2, provide strong evidence supporting that both em /em DM4 -arrestin1 and em /em -arrestin2 function as important regulators during CML progression. The different scenarios of em /em -arrestin1 and em /em -arrestin2 in CML could be explained by the functional redundancy between two proteins. em /em -arrestin1 seems to have a more important role during CML progression, probably due to its nuclear localisation ability (Kang em et al /em , 2005). Here, we reported the expression of both em /em -arrestin1 and em /em -arrestin2 DM4 in the different clinical phases of CML bone marrow cells in patients. Both the expression of em /em -arrestin1 and em /em -arrestin2 was increased in CML patients and did so in a familiar tendency. However, DM4 the enhanced level of em /em -arrestin1 was higher than that of em /em -arrestin2 in the same patient. Meanwhile, downregulated expression of em /em -arrestin2 had less effect on K562 cells than in K562 cells knocked down em /em -arrestin1 expression (Physique 2). Together with our previous interests in em /em -arrestin1 in malignant tumours (Zou em et al /em , 2008; Liu em et al /em , 2011) we selected em /em -arrestin1 for further study, and found an epigenetic regulatory role for em /em -arrestin1. The role of em /em -arrestin2 in CML cells should be further investigated in multiple ways, and for a detailed understanding of the DM4 molecular mechanisms of CML. Enhancer of zeste homologue 2 is one of the composed PRC2 parts in the PcG protein family. PcG proteins could bind with DNA and form DNA-protein complexes, and then transduce the signals (Saurin em et al /em , 2001; Negre em et al /em , 2006; Papp and Muller, 2006). EZH2 is known to be involved in the DM4 progression of prostate cancer (Varambally em et al /em , 2002), regulation of CD11b in ATRA-induced HL-60 differentiation (Tang em et al /em , 2009), some somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-centre origin (Morin em et al /em , 2010) as well as EZH2 governor B cell development through histone H3 methylation and IgH rearrangement (Su em et al /em , 2003). However, whether EZH2 was involved in CML was unclear. Our findings proved that EZH2 is the scaffold partner of em /em -arrestin1 to form the protein complex to mediate histone H4 acetylation, and thus further regulate CML cells progression. Moreover, we also noticed that recruitment of Rabbit Polyclonal to OR4L1 EZH2 at the promoter regions of BCR/ABL was decreased to some extent when em /em -arrestin1 knocked down (data not shown). The detailed binding information and mechanism of EZH2 with em /em -arrestin1 should be further studied. In summary, our study unravels the function of em /em -arrestin1 and further illustrates the mechanism by which em /em -arrestin1 participates in epigenetic regulation in haematological malignancies. We have exhibited that em /em -arrestin1 functions as an important regulator of PcG proteins, which is usually of great significance for PcG-mediated epigenetic regulation. Future investigations should focus on the better understanding of the mechanisms through which PcG is usually regulated by em /em -arrestin1 in the context of hematopoietic malignant diseases. Acknowledgments We thanked Professor Gang Pei for kindly providing lentivirus constructs, thanked Professor Tong-Chuan He, Professor Weihong Song, Dr Rongxi Yang and Dr Shan Jiang for helpful discussion and manuscript reviewing. This study was.