Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Nov 1;49(5):2431-2441.
doi: 10.1042/BST20210772.

Chemical biology approaches to study histone interactors

Antony J Burton  1 , Ghaith M Hamza  1   2 , Andrew X Zhang  1 , Tom W Muir  3
Affiliations
Review

Chemical biology approaches to study histone interactors

Antony J Burton et al. Biochem Soc Trans. .

Abstract

Protein-protein interactions (PPIs) in the nucleus play key roles in transcriptional regulation and ensure genomic stability. Critical to this are histone-mediated PPI networks, which are further fine-tuned through dynamic post-translational modification. Perturbation to these networks leads to genomic instability and disease, presenting epigenetic proteins as key therapeutic targets. This mini-review will describe progress in mapping the combinatorial histone PTM landscape, and recent chemical biology approaches to map histone interactors. Recent advances in mapping direct interactors of histone PTMs as well as local chromatin interactomes will be highlighted, with a focus on mass-spectrometry based workflows that continue to illuminate histone-mediated PPIs in unprecedented detail.

Keywords: chemical biology; chromatin; epigenetics; mass spectrometry; post translational modification; protein–protein interactions.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.. The nucleosome and histone post-translational modifications.
a. X-ray crystal structure of the nucleosome core particle (PDB: 1kx5) displaying DNA wrapped around an octameric core of histone proteins H3, H4, H2A, H2B. b. Selected examples of histone PTM chemotypes. c. Histone PTMs are deposited by writers, interrogated by readers, and removed by erasers.
Figure 2.
Figure 2.. Mapping histone PTMs by mass spectrometry.
Mass spectrometry workflows for the quantitative analysis of selected hPTMs on histone H3 and H4 – middle-down proteomics with HILIC chromatography (left) and Affi-BAMS with MALDI-TOF MS (right).
Figure 3.
Figure 3.. Proximity labeling in chromatin.
a. BioID uses an engineered biotin ligase (BirA*) to generate AMP-biotin esters that react with proximal lysines. When fused to a target histone (blue) and combined with quantitative proteomics workflows, local interactomes can be determined. b. ChromID fuses BirA* to selected hPTM reader domains (green), enabling local interactomes to be determined while avoiding direct fusion to histone proteins.
Figure 4.
Figure 4.. In-situ chromatin interactomics.
Protein trans-splicing installs a hPTM or mutation with an adjacent diazirine and biotin affinity handle. Upon UV irradiation, interacting proteins are covalently bound to the modified histone and can be identified by quantitative proteomics.
See this image and copyright information in PMC

References

    1. Luger K, Mäder AW, Richmond RK, Sargent DF, Richmond TJ. Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature. 1997;389(6648):251–60. - PubMed
    1. Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res. 2011;21(3):381–95. - PMC - PubMed
    1. Kouzarides T Chromatin modifications and their function. Cell. 2007;128(4):693–705. - PubMed
    1. Muller MM, Muir TW. Histones: at the crossroads of peptide and protein chemistry. Chem. Rev. 2015;115(6):2296–349. - PMC - PubMed
    1. Venkatesh S, Workman JL. Histone exchange, chromatin structure and the regulation of transcription. Nat. Rev. Mol. Cell Biol. 2015;16(3):178–89. - PubMed

Publication types

MeSH terms