Skip to content
DraconiticResearch
Search Sources API
203,234 studies31 sourcesUpdated 35 min ago
Peer-reviewedCC BY 4.0Nature genetics

Intrinsically disordered regions restrain genomic targeting of RNA and histone demethylases in mammals and plants

  • Liudan Jiang1,2,3
  • Long Zhao1,2,3
  • Jiangbo Wei1,4
  • Bochen Jiang1,5,6
  • Yu Xiao1,6,7
  • Fan Yang1,2
  • Xiaolin Zeng1,2
  • Chuan He1,2,8,9
9 affiliations
  1. 1Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA
  2. 2Howard Hughes Medical Institute, Chicago, IL 60637, USA
  3. 3These authors contributed equally
  4. 4Department of Chemistry, Department of Biological Sciences, and Cancer Science Institute, National University of Singapore, Singapore
  5. 5School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China
  6. 6Sycamore Research Institute of Life Sciences, Shanghai, 201203, China
  7. 7Department of Chemistry, Fudan University, Shanghai, 200438, China
  8. 8Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA
  9. 9Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA
Read full textDOICite

Abstract

Intrinsically disordered regions (IDRs) are widely recognized as facilitators of chromatin regulation. However, their potential role as regulatory restraints remains poorly understood. Here, we reveal that the C-terminal IDR of mammalian ALKBH5 anchors its main activity to mRNA, limiting chromatin engagement in mouse embryonic stem cells (mESCs). IDR deletion redirects ALKBH5 to chromatin-associated non-coding RNAs, driving widespread chromatin opening and transcriptional activation. This mechanism extends to histone demethylases, where IDR deletion also results in broad removal of repressive histone marks, leading to increased chromatin accessibility and activation of transposable elements (TEs). Building on these insights, we applied IDR deletion to engineer ALKBH5 and its plant homologs. Overexpression of these IDR-deleted ALKBH5 demethylases enhanced Arabidopsis root growth and markedly increased rice yield. Our findings uncover a conserved role for IDRs in restraining chromatin access by RNA and histone demethylases and establish a strategy to reprogram chromatin through endogenous plant proteins for crop improvement.

Related

  1. Molecular Grammar of Intrinsically Disordered Regions: How Sequence and Context Shape Biomolecular Condensation and Disease
    Wei Liu, Sulin Lou
    BiomoleculesPeer-reviewedCC BYFull textGeneral biochemistryEurope PMC
  2. MgATP/MgADP-dependent conformational dynamics and intrinsically disordered regions of vascular KATP channels revealed by cryoEM
    C. M. Driggers, Y.-Y. Kuo, Z. Yang +4
    bioRxivPreprintCC BY-NCFull textMolecular biology & gene regulationbioRxiv
  3. Exitron-type splicing of intrinsically disordered regions recurs across jawed vertebrates despite sequence divergence: donor-proximal cis control in TARDBP
    T. Yamagishi, S. Koide, G. Toyama +5
    bioRxivPreprintCC BY-NC-NDFull textMolecular biology & gene regulationbioRxiv
  4. Intrinsically disordered regions of Src and Abl kinases contribute to membrane binding
    Svenja de Buhr, Julia P. Steringer, Irem Demir +11
    Journal of Biological ChemistryPeer-reviewedCC BY 4.0Full textMolecular biology & gene regulationCrossrefPMC
  5. The intrinsically disordered N-terminal region of eIF5B nucleates RNA-driven phase separation
    B. K. Bodley-Gomes, M. T. Marr
    bioRxivPreprintAll rights reservedFull textGeneral biochemistrybioRxiv

Cite

BibTeXRIS
BibTeX
@article{jiang2026intrinsically,
  title = {{Intrinsically disordered regions restrain genomic targeting of RNA and histone demethylases in mammals and plants}},
  author = {Liudan Jiang and Long Zhao and Jiangbo Wei and Bochen Jiang and Yu Xiao and Fan Yang and Xiaolin Zeng and Chuan He},
  journal = {Nature genetics},
  year = {2026},
  month = jul,
  doi = {10.1038/s41588-026-02685-w},
  url = {https://doi.org/10.1038/s41588-026-02685-w},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Intrinsically disordered regions restrain genomic targeting of RNA and histone demethylases in mammals and plants
AU  - Liudan Jiang
AU  - Long Zhao
AU  - Jiangbo Wei
AU  - Bochen Jiang
AU  - Yu Xiao
AU  - Fan Yang
AU  - Xiaolin Zeng
AU  - Chuan He
PY  - 2026
DA  - 2026/07/23
JO  - Nature genetics
DO  - 10.1038/s41588-026-02685-w
UR  - https://doi.org/10.1038/s41588-026-02685-w
AB  - Intrinsically disordered regions (IDRs) are widely recognized as facilitators of chromatin regulation. However, their potential role as regulatory restraints remains poorly understood. Here, we reveal that the C-terminal IDR of mammalian ALKBH5 anchors its main activity to mRNA, limiting chromatin engagement in mouse embryonic stem cells (mESCs). IDR deletion redirects ALKBH5 to chromatin-associated non-coding RNAs, driving widespread chromatin opening and transcriptional activation. This mechanism extends to histone demethylases, where IDR deletion also results in broad removal of repressive histone marks, leading to increased chromatin accessibility and activation of transposable elements (TEs). Building on these insights, we applied IDR deletion to engineer ALKBH5 and its plant homologs. Overexpression of these IDR-deleted ALKBH5 demethylases enhanced Arabidopsis root growth and markedly increased rice yield. Our findings uncover a conserved role for IDRs in restraining chromatin access by RNA and histone demethylases and establish a strategy to reprogram chromatin through endogenous plant proteins for crop improvement.
SN  - 1061-4036
SN  - 1546-1718
ER  -