The interaction of positively charged N-terminal histone tails with nucleosomal DNA plays an important role in chromatin assembly and regulation, modulating their susceptibility to post-translational modifications and recognition by chromatin-binding proteins. Here, we report residue-specific N NMR relaxation rates for histone H4 tails in reconstituted nucleosomes. These data indicate that H4 tails are strongly dynamically disordered, albeit with reduced conformational flexibility compared to a free peptide with the same sequence. Remarkably, the NMR observables were successfully reproduced in a 2-μs MD trajectory of the nucleosome. This is an important step toward resolving an apparent inconsistency where prior simulations were generally at odds with experimental evidence on conformational dynamics of histone tails. Our findings indicate that histone H4 tails engage in a fuzzy interaction with nucleosomal DNA, underpinned by a variable pattern of short-lived salt bridges and hydrogen bonds, which persists at low ionic strength (0-100 mM NaCl).
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994933 | PMC |
| http://dx.doi.org/10.1002/anie.202012046 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
TGM2-mediated histone serotonylation promotes HCC progression via MYC signalling pathway.
J Hepatol
January 2025
Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan 430030, China; Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan 430030, China; Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, , Chinese Academy of Medical Sciences, Wuhan 430030, China. Electronic address:
Background & Aims: Hepatocellular carcinoma (HCC) is an aggressive malignancy with few effective treatment options. H3Q5ser, a serotonin-based histone modification mediated by transglutaminase 2 (TGM2), affects diverse biological processes, such as neurodevelopment. The role of TGM2-mediated H3Q5ser in HCC progression remains unclear.
View Article and Find Full Text PDFCG modeling of nucleosome arrays reveals the salt-dependent chromatin fiber conformational variability.
J Chem Phys
January 2025
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
Eukaryotic DNA is packaged in the cell nucleus into chromatin, composed of arrays of DNA-histone protein octamer complexes, the nucleosomes. Over the past decade, it has become clear that chromatin structure in vivo is not a hierarchy of well-organized folded nucleosome fibers but displays considerable conformational variability and heterogeneity. In vitro and in vivo studies, as well as computational modeling, have revealed that attractive nucleosome-nucleosome interaction with an essential role of nucleosome stacking defines chromatin compaction.
View Article and Find Full Text PDFStructural basis for the inhibition of PRC2 by active transcription histone posttranslational modifications.
Nat Struct Mol Biol
January 2025
Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Polycomb repressive complex 2 (PRC2) trimethylates histone H3 on K27 (H3K27me3) leading to gene silencing that is essential for embryonic development and maintenance of cell identity. PRC2 is regulated by protein cofactors and their crosstalk with histone modifications. Trimethylated histone H3 on K4 (H3K4me3) and K36 (H3K36me3) localize to sites of active transcription and inhibit PRC2 activity through unknown mechanisms.
View Article and Find Full Text PDFDevelopment of nucleus-targeted histone-tail-based photoaffinity probes to profile the epigenetic interactome in native cells.
Nat Commun
January 2025
School of Food and Biological Engineering, Engineering Research Center of Bio-process, Ministry of Education, Key Laboratory of Animal Source of Anhui Province, Hefei University of Technology, Hefei, 230009, China.
Dissection of the physiological interactomes of histone post-translational modifications (hPTMs) is crucial for understanding epigenetic regulatory pathways. Peptide- or protein-based histone photoaffinity tools expanded the ability to probe the epigenetic interactome, but in situ profiling in native cells remains challenging. Here, we develop a nucleus-targeting histone-tail-based photoaffinity probe capable of profiling the hPTM-mediated interactomes in native cells, by integrating cell-permeable and nuclear localization peptide modules into an hPTM peptide equipped with a photoreactive moiety.
View Article and Find Full Text PDFIntroductory Analysis and Validation of CUT&RUN Sequencing Data.
J Vis Exp
December 2024
Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center; Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center;
The CUT&RUN technique facilitates detection of protein-DNA interactions across the genome. Typical applications of CUT&RUN include profiling changes in histone tail modifications or mapping transcription factor chromatin occupancy. Widespread adoption of CUT&RUN is driven, in part, by technical advantages over conventional ChIP-seq that include lower cell input requirements, lower sequencing depth requirements, and increased sensitivity with reduced background signal due to a lack of cross-linking agents that otherwise mask antibody epitopes.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!