Requirement of CRTC1 coactivator for hepatitis B virus transcription

Tang, Hei-Man Vincent; Gao, Wei-Wei; Chan, Chi-Ping; Cheng, Yun; Chaudhary, Vidyanath; Deng, Jian-Jun; Yuen, Kit-San; Wong, Chun-Ming; Ng, Irene Oi-Lin; Kok, Kin-Hang; Zhou, Jie; Jin, Dong-Yan

Our results supported the model in which CRTCs cooperate with CREB to activate the preS2 promoter ( Figure 5 ). We also showed the recruitment of CRTCs to cccDNA and preS2-CRE in pHBV1.3D-transfected cells (Figure 2) . These findings support a more direct involvement of CRTCs in HBV transcription from cccDNA. However, an indirect stimulatory role of CRTC2 on the core promoter mediated through PGC1␣ has also been suggested (13) . We also observed a modest activation of the preS1 and core promoters by all three CRTCs (Supplementary Figure S1) . However, since no CRE has been found in these promoters, their general and mild activation by CRTCs is likely mediated indirectly through a CREB-regulated gene such as PGC1␣. Thus, the influence of CRTCs on HBV transcription might be exerted through both direct activation as demonstrated in our study and an indirect effect as suggested for CRTC2 (13) . Particularly, the stimulatory effect of CRTCs on pgRNA expression (Figure 3 ) could be mediated through the core promoter.