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. Author manuscript; available in PMC: 2012 Apr 29.
Published in final edited form as: Cell. 2011 Apr 14;145(3):423–434. doi: 10.1016/j.cell.2011.03.022

Figure 7. Tet1 and Apobec1 are Involved in Neuronal Activity-Induced Region-Specific Demethylation in the Adult Mouse Brain.

Figure 7

(A to C) Effects of AAV-mediated shRNA knock-down of endogenous Tet1 and Apobec1 on ECS-induced CpG demethylation of Bdnf IX (A), Fgf1B (B) and Fgf1G (C) promoters. Engineered AAV viruses expressing control shRNA (CTL), two shRNAs against mouse Tet1 (Tet1-1 and Tet1-2), and one shRNA against mouse Apobec1 (Ap1-5), were stereotaxically injected into the dentate gyrus of adult mice. One week after viral injection, animals were subjected to ECS or sham treatment. Dentate gyrus tissue was micro-dissected 4 hrs later for analysis. Values represent mean ± SEM (n = 3–6 animals for each condition; **: P < 0.01; *: P < 0.05; Student’s t-test).

(D and E) Effects of Tet1 and Apobec1 knock-down on ECS-induced isoform-specific expression of Bdnf and Fgf1 in the adult dentate gyrus. Same groups of animals as in (A to C) were examined. Values represent mean ± SEM (*: P < 0.05; Student’s t-test).

(F) Demethylation of 5hmC-GFP DNA fragments after transfection into primary hippocampal neurons in culture. Shown is a histogram of clone distribution of the percentage of demethylated 5hmCs in 5hmC-GFP DNA fragments retrieved 7 days after transfection. A distributive Poisson model (λ = 6.2%) is shown by a black curve.