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XB-ART-60650
iScience 2024 Apr 19;274:109458. doi: 10.1016/j.isci.2024.109458.
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Glutamylation of Npm2 and Nap1 acidic disordered regions increases DNA mimicry and histone chaperone efficiency.

Lorton BM , Warren C , Ilyas H , Nandigrami P , Hegde S , Cahill S , Lehman SM , Shabanowitz J , Hunt DF , Fiser A , Cowburn D , Shechter D .


Abstract
Histone chaperones-structurally diverse, non-catalytic proteins enriched with acidic intrinsically disordered regions (IDRs)-protect histones from spurious nucleic acid interactions and guide their deposition into and out of nucleosomes. Despite their conservation and ubiquity, the function of the chaperone acidic IDRs remains unclear. Here, we show that the Xenopus laevis Npm2 and Nap1 acidic IDRs are substrates for TTLL4 (Tubulin Tyrosine Ligase Like 4)-catalyzed post-translational glutamate-glutamylation. We demonstrate that to bind, stabilize, and deposit histones into nucleosomes, chaperone acidic IDRs function as DNA mimetics. Our biochemical, computational, and biophysical studies reveal that glutamylation of these chaperone polyelectrolyte acidic stretches functions to enhance DNA electrostatic mimicry, promoting the binding and stabilization of H2A/H2B heterodimers and facilitating nucleosome assembly. This discovery provides insights into both the previously unclear function of the acidic IDRs and the regulatory role of post-translational modifications in chromatin dynamics.

PubMed ID: 38571760
PMC ID: PMC10987829
Article link: iScience
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: aopep h2ac21 h2bc21 nap1l1 nasp npm2 ttll4
GO keywords: histone chaperone activity
Antibodies: Nap1l1 Ab2 Npm2 Ab1 Npm2 Ab2


Article Images: [+] show captions
References [+] :
Aguilar-Gurrieri, Structural evidence for Nap1-dependent H2A-H2B deposition and nucleosome assembly. 2016, Pubmed