Differential expression of H2A isoforms contribute to tissue and lineage specificity with HIST2H2AC as a potential cancer biomarker

Abstract

Recent advancements in the field of histone biology imply non-redundancy in the function of histone H2A isoforms; however, the expression of H2A isoforms in various normal tissue types, the correlation among organs and tumor/tumor type-specific expression remain poorly investigated. The profiling of sixteen H2A isoforms in eleven different normal human tissue types strongly suggests their tissue-specific or predominant expression. Further, clustering analysis shows a lineage-specific correlation of H2A isoforms. In continuation, the expression analysis in twelve human tumor types shows overexpression of HIST2H2AC. Moreover, overexpression was observed exclusively in tumor samples but not with fetal samples; highlighting the cancer-specific association of HIST2H2AC. Further, in silico analysis of TCGA pan-cancer data also showed tumor-specific over-expression of the HIST2H2AC isoform. Our findings provide insights into tissue-type-specificity of histone H2A isoforms expression patterns and advance our understanding of their importance in lineage specification and cancer.

Beyond the Usual Suspects: Examining the Role of Understudied Histone Variants in Breast Cancer

“…Indeed, studies now show that histone genes within histone gene clusters are differentially expressed and are not only 'replication-independent', but their expression is cell-type-and tissue-typespecific [7,8,59,[72][73][74]. For example, HIST1H2AE shows high expression in breast tissue, indicating its significance in breast tissue specificity [75]. The differential expression of histone variants across cell types suggests their diverse physiological roles [8,59], some of which are outlined below.…”