Extensive and systematic rewiring of histone post-translational modifications in cancer model systems

ABSTRACT: Histone post-translational modifications (PTMs) generate a complex combinatorial code that regulate gene expression and nuclear functions, and whose deregulation has been documented in different types of cancers. Therefore, the availability of relevant culture models that can be manipulated and that retain the epigenetic features of the tissue of origin is absolutely crucial for studying epigenetic mechanisms underlying cancer, as well as for testing epigenetic drugs and uncovering possible epigenetic biomarkers. In this study, we took advantage of quantitative mass spectrometry to comprehensively profile histone PTMss in patient tumor tissues, primary cultures and cell lines from two representative tumor models, breast cancer and glioblastoma, revealing a dramatic and systematic rewiring of histone marks in cell culture conditions, which include a decrease of H3K27me3, H3K79me1/me2 and H3K9ac/K14ac, and an increase of H3K36me1/me2. While some changes occurr in short-term primary cultures, most of them are instead time-dependent and appear only in long-term cultures. Remarkably, such change mostly revert in cell line- and primary cell-derived in vivo xenograft models. Our results support the use of short-term cultures and xenografts models as the most representative models of in vivo epigenetic processes, and suggest cautions when using cell lines and long-term primary cultures for epigenetic investigations.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain, Permanent Cell Line Cell

DISEASE(S): Brain Cancer,Malignant Neoplasm Of Ovary,Breast Cancer

SUBMITTER: Roberta Noberini  

LAB HEAD: Tiziana, Bonaldi

PROVIDER: PXD007235 | Pride | 2018-04-06

REPOSITORIES: Pride