Fig. 3: TTC7A deficiency deregulates the transcriptional activity of promoters and enhancers of active genes. | Cell Discovery

Fig. 3: TTC7A deficiency deregulates the transcriptional activity of promoters and enhancers of active genes.

From: Tetratricopeptide repeat domain 7A is a nuclear factor that modulates transcription and chromatin structure

Fig. 3

a Principal component analysis (PCA) representing the variation between transcription profile of four controls (C1 to C4) and six patients (P1 to 4_E71K, P */L478P, and P */A524V). b Heatmaps for differently expressed transcripts in the four controls and six patients’ B lymphoblastoid cell lines (same as A). Transcription level was determined by HTA-2 microarray. Scale is relative to the population average (green: low; red: high) and p < 0.05; Student's t test. c Metaplots of TTC7A occupancy in control cells for all transcripts classified according to the expression in four groups containing the same number of transcripts, from lowest quartile 1 (Q1) to highest quartile 4 (Q4). RPM: reads per million mapped reads. d Proportion of differentially expressed transcripts in TTC7A-deficent cells (fold change > 1.2 and p-value < 0.05 between control and patients’ cells) among overall transcripts classified by quartiles. e and f Average profile plots of H3K27ac or H3K27me3 epigenetic markers at TSS regions of differentially expressed transcripts. Normalized level of H3k27ac and H3k27me3 in control and patients is depicted for up- and downregulated set of genes, e and f, respectively. g ChIP-quantitative PCR showing the amount of H3k27ac and H3k27me3 in two regions abnormally increased in patient cells. Left: a region highly acetylated, and right: a region highly methylated in patient cells. PCR quantification was obtained using a standard curve from the input DNA material. The fold enrichment was determined relatively to the level of control immunoglobulin ChIP. One control and two patients (P2_E71K and P */L478P) were assessed in non transduced and Flag-tagged WT_TTC7A transduced cells. Mean of two independent experiments ± SEM in duplicate. Unpaired t test; *p-value < 0.05. h Metaplots of H3K27ac occupancy at active, repressed, and unchanged enhancers in patient cells. Enhancers regions were set to be 2 kb upstream of TSS (transcription starting sites) and 10 kb downstream of TTS (transcription termination sites). i Box plots showing log2-fold change (FC) of transcripts level of genes 0–20, 20–60, and 60–80 kb nearby active, repressed, and unchanged enhancers in patient cells

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