Figure 6. ACTL6A overexpression leads to redistribution of H3K27me3 and activation of SCC genes.

(A) Heat maps for H3K27me3 CUT&RUN differential 5kb-bins between primary human keratinocytes overexpressing ACTL6A and vector-control. CPM : counts per million. n=2 experiments.

(B) Profiles over TSS with decreased (top) and increased (bottom) H3K27me3 levels upon ACTL6A-overexpression versus vector control by CUT&RUN. Right: H3K4me3 ChIP-seq profiles of human keratinocytes (ENCODE). CPM: counts per million.

(C) Scatterplot of H3K27me3 and RNA fold-changes for genes with differential H3K27me3 levels upon ACTL6A-overexpression. Color codes: H3K4me3 levels, high versus low or negative (neg).

(D) Heatmap showing ACTL6A-dependent PRC target genes with corresponding transcriptional changes in SCC tumors. H3K27me3: CUT&RUN as in (A). RNA: HNSC (head-and-neck SCC) and LUSC (lung SCC) tumor versus normal tissue from GEPIA 2.

(E) Genome browser tracks at bivalent WNT7B gene upon ACTL6A-overexpression (+) compared to vector control (−).

(F) WNT7B medium expression levels in tumors and paired normal tissues across various cancers. Data from GEPIA 2. TPM: transcripts per million. HNSC: head-and-neck SCC. LUSC: lung SCC. BLCA: bladder urothelial carcinoma. CESC: cervical SCC and endocervical adenocarcinoma. ESCA: esophageal carcinoma. LUAD: lung adenocarcinoma. CHOL: cholangiocarcinoma. LGG: brain lower grade glioma. PRAD: prostate adenocarcinoma. PAAD: pancreatic adenocarcinoma. BRCA: breast invasive carcinoma. OV: ovarian serous cystadenocarcinoma. THYM: thymoma. THCA: thyroid carcinoma. UCEC: uterine corpus endometrial carcinoma. GBM: glioblastoma multiforme. STAD: stomach adenocarcinoma. SKCM: skin cutaneous melanoma.

(G) Model for ACTL6A-amplification driven oncogenic mechanism in SCCs. Amplification or overexpression of ACTL6A leads to full occupancy of BAF complexes giving rise to two mechanisms promoting SCC initiation and maintenance.