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Fig. 6 | Clinical Epigenetics

Fig. 6

From: BDNF exon IV promoter methylation and antidepressant action: a complex interplay

Fig. 6

Proposed molecular mechanism for methylation-specific BDNF exon IV transcriptional activation. CREB, a known transcriptional factor binds to cAMP response element (CRE) on BDNF exon IV promoter and upregulate transcription by recruiting co-activators like CREB-binding protein (CBP). MeCP2 binds across genome, preferably to methylated CpGs and functions as chromatin modifier. Site-specific methylation of BDNF exon IV promoter increases MeCP2 occupancy at the methylated CpGs. MeCP2 and CREB form a transcriptional activating complex. No increase in CREB–CRE interaction was observed, if methylated CpG is far from CRE as with CpG-87 (a) or at the 3′ end of CRE as observed with CpG-35 (b). Methylation at CpG-39 allows the recruitment of MeCP2-CREB protein complex and increases the transcriptional activity at BDNF exon IV promoter (c). Illustration was created with BioRender.com

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