Fig. 6: CREB1 binds in a methylation-sensitive manner to IAPLTR1/1a elements and contributes to repeat activity. | Nature Genetics

Fig. 6: CREB1 binds in a methylation-sensitive manner to IAPLTR1/1a elements and contributes to repeat activity.

From: Evidence that direct inhibition of transcription factor binding is the prevailing mode of gene and repeat repression by DNA methylation

Fig. 6

a, Single-locus example illustrating DNA methylation-sensitive binding of CREB1 (blue tracks, ChIP–seq) in WT and DNMT–TKO (TKO) neurons. CREB1 motifs shown in the motif track. Chromatin accessibility (black tracks, ATAC–seq) for WT, DNMT–TKO and CREB1–KO in DNMT–TKO neurons. Top track indicates CpG methylation (black dots) in WT neurons. Chr7: 41118130−41118764. b, Changes in CREB1 binding between DNMT–TKO and WT neurons grouped according to their motif methylation in WT neurons. n, number of CREB1 sites indicated for each bin. Boxplots as in Fig. 2d. c, Changes in chromatin accessibility (top, ATAC–seq), POL2 binding (middle, ChIP–seq) and CREB1 binding (bottom, ChIP–seq) in WT and DNMT–TKO neurons at IAPLTR1/1a elements gaining expression in the absence of DNA methylation (RNA-seq, FDR < 0.05 and log2FC ≥ 1). Signal is centered at the start site of IAP elements. Orange bars denote average width of the 5' LTR and dashed lines average length of an entire IAP element, including the 5' and 3' LTR regions. Only uniquely mapping reads are considered. Replicates per condition are combined in each composite plot. n, number of elements. d, Genic example (Fsip2l) of CREB1-mediated activation following loss of DNA methylation. CpG methylation and CRE motifs are indicated; CREB1 ChIP–seq, blue tracks; gray bar indicates the promoter region methylated in WT neurons. ChrX: 48838466−48880713. e, ATAC–seq signal or RNA expression levels of IAPLTR1 (n = 746) or 1a (n = 884) elements in WT or DNMT–TKO neurons with (orange) or without (yellow) functional CREB1 gene at elements derepressed in the absence of DNA methylation (FDR < 0.05 and FC ≥ 2). Only reads mapping uniquely to the reference genome were considered. ATAC–seq reads counted in 5' LTRs were summed for each replicate (n = 3). Replicates (n = 2) of RNA-seq reads counted in the IAPLTR1/1a element were combined by condition. Boxplots as in Fig. 2d. Statistical significance calculated using two-sided t-test, and P values are shown.

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