Incorporation of different H3 histone isoforms/variants have been reported to differentially regulate gene expression via alteration in chromatin organization during diverse cellular processes. However, the differential expression of highly conserved histone H3.2 genes, H3C14 and H3C13 in human cancer has not been delineated. In this study, we investigated the expression of H3.2 genes in primary human gastric, brain, breast, colon, liver, and head and neck cancer tissues and tumor cell lines. The data showed overexpression of H3.2 transcripts in tumor samples and cell lines with respect to normal counterparts. Furthermore, TCGA data of individual and TCGA PANCAN cohort also showed significant up-regulation of H3.2 genes. Further, overexpressed H3C14 gene coding for H3.2 protein was regulated by FOXC1 transcription factor and G4-cassette in gastric cancer cell lines. Elevated expression of FOXC1 protein and transcripts were also observed in human gastric cancer samples and cell lines. Further, FOXC1 protein was predominantly localized in the nuclei of neoplastic gastric cells compared to normal counterpart. In continuation, studies with EGF induction, FOXC1 knockdown, and ChIP-qPCR for the first time identified a novel axis, EGFR-FOXC1-H3C14 for regulation of H3C14 gene overexpression in gastric cancer. Therefore, the changes the epigenomic landscape due to incorporation of differential expression H3 variant contributes to change in gene expression pattern and thereby contributing to pathogenesis of cancer.

据报道，在不同的细胞过程中，通过结合染色质组织，不同的H3组蛋白同工型/变异体的结合可差异调节基因的表达。然而，尚未描述高度保守的组蛋白H3.2基因，H3C14和H3C13在人类癌症中的差异表达。在这项研究中，我们调查了H3.2基因在原发性人胃癌，脑癌，乳腺癌，结肠癌，肝癌，头颈癌组织和肿瘤细胞系中的表达。数据显示相对于正常对应物，H3.2转录本在肿瘤样品和细胞系中过表达。此外，个体和TCGA PANCAN队列的TCGA数据也显示出H3.2基因的显着上调。此外，过表达H3的H3C14基因编码。胃癌细胞系中FOXC1转录因子和G4-盒调控2蛋白的表达。在人胃癌样品和细胞系中还观察到FOXC1蛋白和转录物的表达升高。此外，与正常对应物相比，FOXC1蛋白主要位于赘生性胃细胞的细胞核中。继续，研究EGF诱导，FOXC1敲低和ChIP-qPCR首次确定了新型轴，EGFR-FOXC1-H3C14，用于调节胃癌中H3C14基因的过表达。因此，由于掺入差异表达H3变体而引起的表观基因组格局的变化有助于基因表达模式的变化，从而有助于癌症的发病。