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Review
. 2019 Nov 20;20(1):245.
doi: 10.1186/s13059-019-1870-5.

Epigenetic modifications of histones in cancer

Zibo Zhao  1   2 , Ali Shilatifard  3   4
Affiliations
Review

Epigenetic modifications of histones in cancer

Zibo Zhao et al. Genome Biol. .

Abstract

The epigenetic modifications of histones are versatile marks that are intimately connected to development and disease pathogenesis including human cancers. In this review, we will discuss the many different types of histone modifications and the biological processes with which they are involved. Specifically, we review the enzymatic machineries and modifications that are involved in cancer development and progression, and how to apply currently available small molecule inhibitors for histone modifiers as tool compounds to study the functional significance of histone modifications and their clinical implications.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Balanced states of transcription maintained by the versatile chromatin proteins and histone modifications. The balanced states of transcription are maintained by the chromatin modifiers and histone modifications. The histone-modifying enzymes are depicted as apples (activation) and oranges (repression) in the two weighing pans respectively. The chromatin states are maintained and balanced by a number of activation marks and repression marks. Histone marks highlighted in bold are considered to be hallmarks of euchromatin (H4K16ac) and heterochromatin (H3K9me3 and H3K27me3) respectively
Fig. 2
Fig. 2
Pharmacological restoration of the epigenetic balance of gene expression in human cancers. a MLL translocation and SEC promote the leukemogenesis in MLL-rearranged leukemia. Enhancing the wild-type MLL1 recruitment to chromatin by hijacking the IL1/IRAK4 and CKII/tasapse1 pathways displaces the MLL chimera and SEC and inhibits leukemogenesis. b MLL3 mutation in the PHD leads to the loss of function of MLL3/COMPASS and decreased enhancer H3K4 methylation. EZH2 inhibition by small molecules (e.g., GSK-126) inhibits EZH2 enzymatic activity and decreases H3K27 methylation to restore the tumor suppressor gene expression. c H3K27M mutation leads to the global increase of H3K27 acetylation and aberrant gene expression. Inhibition of BRD4 by small molecules (e.g., JQ-1) displaces the protein from chromatin and restores the normal-like gene expression and inhibits DIPG from progression
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