Beyond the tail: the consequence of context in histone post-translational modification and chromatin research

Abstract

The role of histone post-translational modifications (PTMs) in chromatin structure and genome function has been the subject of intense debate for more than 60 years. Though complex, the discourse can be summarized in two distinct — and deceptively simple — questions: What is the function of histone PTMs? And how should they be studied? Decades of research show these queries are intricately linked and far from straightforward. Here we provide a historical perspective, highlighting how the arrival of new technologies shaped discovery and insight. Despite their limitations, the tools available at each period had a profound impact on chromatin research, and provided essential clues that advanced our understanding of histone PTM function. Finally, we discuss recent advances in the application of defined nucleosome substrates, the study of multivalent chromatin interactions, and new technologies driving the next era of histone PTM research.

Visualizing histone H4K20me1 in knock-in mice expressing the mCherry-tagged modification-specific intracellular antibody

“…Posttranslational histone modifications play critical roles in development and differentiation through the regulation of genome functions including gene expression, DNA replication, and genome maintenance (Millán-Zambrano et al 2022; Weinzapfel et al 2024). Some modifications, such as histone H3 Lys9 trimethylation (H3K9me3) and Lys27 trimethylation (H3K27me3), are maintained through cell generations to epigenetically sustain a transcriptionally repressive chromatin state (Margueron and Reinberg 2010).…”

Visualizing histone H4K20me1 in knock-in mice expressing the mCherry-tagged modification-specific intracellular antibody

“…Posttranslational histone modifications play critical roles in development and differentiation through the regulation of genome functions including gene expression, DNA replication, and genome maintenance (Millán-Zambrano et al 2022 ; Weinzapfel et al 2024 ). Some modifications, such as histone H3 Lys9 trimethylation (H3K9me3) and Lys27 trimethylation (H3K27me3), are maintained through cell generations to epigenetically sustain a transcriptionally repressive chromatin state (Margueron and Reinberg 2010 ).…”