A recent publication in Epigenetics & Chromatin reports on a comprehensive ‘atlas’ of histone post-translational modifications (PTMs) in 24 commonly used cell lines, the majority of which are cancer cells, and thus provides insight into the chromatin modification status of different cancer types.
Histone acetylation was first described nearly 50 years ago, and since then a variety of histone PTMs, including lysine acetylation, arginine and lysine methylation, phosphorylation and SUMOylation amongst others, have been identified and mapped. Histone PTMs are thought to be involved in a number of cellular processes, such as transcription, DNA repair and replication. As the mis-regulation of these processes is a key factor in the development of cancer, it is important to understand how chromatin is specifically modified in cancer cells.
In this study, Benjamin Garcia, from the University of Pennsylvania, USA, and colleagues applied mass spectrometry based proteomic techniques to determine the relative abundances of histone modifications for 24 cell lines, focussing on histone H3 and H4 in particular. Unsurprisingly, cell lines of similar tissue origin, such as the breast lines MCF7 and MDA-MB231, had similar histone PTM patterns. However, the converse – cell lines originating from different tissues exhibiting different histone PTM patterns – was not always true. For example, SAOS, an osteosarcoma cell line, and U251, a glioblastoma line, shared similar H3 and H4 PTM patterns.
The researchers also used custom microarrays to assess the expression of genes coding for various chromatin modifying enzymes, including histone deacetylases and histone methyltransferases, in each cell line. The results of this genomic analysis supported their proteomic findings.
A particularly interesting result from the proteomic atlas is the enrichment of H3K27me3 (tri-methylation of lysine 27 on histone H3), resulting from the activity of histone-lysine N-methyltransferase EZH2, in the MCF7 and MDA-MB231 breast lines. The authors tested the hypothesis that H3K27me3 is important for the tumourigenicity of cell lines enriched for this modification by injecting either control MDA-MB231 cells or those in which EZH2 had been knocked down (EZH2-KD) into the mammary fat pads of mice. Breast tumours formed by control cells grew rapidly, whereas EZH2-KD cells either resulted in small tumours with reduced growth rates or failed to initiate tumours altogether. These findings highlight the importance of EZH2 and so H3 modifications in tumour development.
By creating this atlas, Garcia and colleagues have provided a helpful resource for the community to further analyse and classify cancer cells.