Fig. 6: AR is a determinant of chromatin association of total and phospho-Ser 301 lamin A/C. | Nature Communications

Fig. 6: AR is a determinant of chromatin association of total and phospho-Ser 301 lamin A/C.

From: Nuclear lamin A/C phosphorylation by loss of androgen receptor leads to cancer-associated fibroblast activation

Fig. 6

A Box violin plots showing the enrichment of narrow peaks of total (Lamin A/C) and phospho-Ser301 (pSer301) lamin A/C binding to chromatin, as assessed by less stringent chromatin preparation followed by ChIP-seq analysis in two independent HDF strains (HDF-2, HDF-1) with shRNA-mediated AR silencing versus control. The box plots violin plots show enrichment of narrow peaks in each condition, with minimum, first quartile (lower bound), median, third quartile (upper bound), maximum values, whiskers up to 1.5 times the interquartile range. B The genomic distribution of unique and overlapping (within 500 bp of summits) peaks of total and phospho-Ser301 lamin A/C. Density heatmaps of the average distributions of total (C) and phospho-Ser301 lamin A/C (D) peaks around the TSS of genes (±3 Kb) in control versus AR silenced (shAR) HDFs. The aggregation plots represent the enrichments peak signals in shAR (red line) versus control (blue line) conditions. E Genomic distribution of phospho-Ser301 peaks associated with genes that are up or down-regulated in AR silenced HDFs. 10% of genes modulated by AR silencing was associated with pSer301 peaks with an overlap that by two-sided Chi-Square test was statistically significant (Supplementary Data S3). F Functional classification of shAR upregulated genes that were associated with pSer301 binding peaks in HDF-2. G Higher resolution genome browser view of phospho-Ser 301 and total lamin A/C binding peaks to the TGFBR1 and PLOD2 CAF effector genes in the HDF-2 and HDF-1 strains plus/minus AR gene silencing. ChIP-seq and ATAC-seq profiles were uploaded onto the EaSeq tool (https://easeq.net/). Position of the transcription start site (TSS) and part of the transcribed regions (solid lines) are indicated. The boxed area indicates the regulatory region of the gene around the TSS marked by experimentally determined H3K27Ac ChIP-seq profiles in parallel with those derived from the human dermal fibroblast profiles in ENCODE. Analysis of other genes of interest is provided in Supplementary Fig. 6D. Source data for relevant pie chart are in the Source Data file.

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