TY - JOUR
T1 - Histone H3 Tail Modifications Alter Structure and Dynamics of the H1 C-Terminal Domain Within Nucleosomes
AU - Das, Subhra Kanti
AU - Kumar, Ashok
AU - Hao, Fanfan
AU - Cutter DiPiazza, Amber R.
AU - Fang, He
AU - Lee, Tae Hee
AU - Hayes, Jeffrey J.
N1 - Funding Information:
The work was supported by National Institutes of Health Grants R01GM052426 and R35GM149420 (to J.J.H.), T32GM068411 (to A.R.C.D.), R01GM123164, R01GM130793, and R35GM148208 (to T.L.). We also acknowledge support from NIH S10-OD021489-01A1.
Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/10/1
Y1 - 2023/10/1
N2 - The highly positively charged and intrinsically disordered H1 C-terminal domain (CTD) undergoes extensive condensation upon binding to nucleosomes, and stabilizes nucleosomes and higher-order chromatin structures but its interactions in chromatin are not well defined. Using single-molecule FRET we found that about half of the H1 CTDs in H1-nucleosome complexes exhibit well-defined FRET values indicative of distinct, static conformations, while the remainder of the population exhibits exchange between multiple defined FRET structures. Moreover, crosslinking studies indicate that the first 30 residues of the H1 CTD participate in relatively localized contacts with the first ∼25 bp of linker DNA, and that two separate regions in the CTD contribute to H1-dependent organization of linker DNA. Finally, we show that acetylation mimetics within the histone H3 tail markedly reduce the overall extent of H1 CTD condensation and significantly increase the fraction of H1 CTDs undergoing dynamic exchange between FRET states. Our results indicate the nucleosome-bound H1 CTD adopts loosely defined structures that exhibit significantly enhanced dynamics and decondensation upon epigenetic acetylation within the H3 tail.
AB - The highly positively charged and intrinsically disordered H1 C-terminal domain (CTD) undergoes extensive condensation upon binding to nucleosomes, and stabilizes nucleosomes and higher-order chromatin structures but its interactions in chromatin are not well defined. Using single-molecule FRET we found that about half of the H1 CTDs in H1-nucleosome complexes exhibit well-defined FRET values indicative of distinct, static conformations, while the remainder of the population exhibits exchange between multiple defined FRET structures. Moreover, crosslinking studies indicate that the first 30 residues of the H1 CTD participate in relatively localized contacts with the first ∼25 bp of linker DNA, and that two separate regions in the CTD contribute to H1-dependent organization of linker DNA. Finally, we show that acetylation mimetics within the histone H3 tail markedly reduce the overall extent of H1 CTD condensation and significantly increase the fraction of H1 CTDs undergoing dynamic exchange between FRET states. Our results indicate the nucleosome-bound H1 CTD adopts loosely defined structures that exhibit significantly enhanced dynamics and decondensation upon epigenetic acetylation within the H3 tail.
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U2 - 10.1016/j.jmb.2023.168242
DO - 10.1016/j.jmb.2023.168242
M3 - Article
C2 - 37619707
AN - SCOPUS:85169000511
SN - 0022-2836
VL - 435
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 19
M1 - 168242
ER -