RID is required for both repeat-induced point mutation and nucleation of a novel transitional heterochromatic state for euchromatic repeats

Zhen He; Nannan Wu; Ruonan Yao; Huawei Tan; Yingying Sun; Jingxuan Chen; Lan Xue; Xiaonan Chen; Sihai Yang; Laurence D. Hurst; Long Wang; Ju Huang

doi:10.1093/nar/gkaf263

RID is required for both repeat-induced point mutation and nucleation of a novel transitional heterochromatic state for euchromatic repeats

Zhen He, Nannan Wu, Ruonan Yao, Huawei Tan, Yingying Sun, Jingxuan Chen, Lan Xue, Xiaonan Chen, Sihai Yang, Laurence D. Hurst, Long Wang, Ju Huang

Research output: Contribution to journal › Article › peer-review

2 Citations (SciVal)

Abstract

To maintain genome integrity, repeat sequences are subject to heterochromatin inactivation and, in Neurospora, repeat-induced point mutation (RIP). The initiating factors behind both are poorly understood. We resolve the paradoxical observation that newly introduced Repeat-Linker-Repeat (R-L-R) constructs require RID alone for RIP, while genomic repeats are RIPed in the absence of RID, showing that eu- and hetero- chromatic repeats are handled differently, the latter additionally requiring DIM-2. The differences between mechanisms associated with older and newer duplicates caution against extrapolation from mechanisms inferred from model experimental systems. Additionally, while chromatin status affects RIP, we also show that RID, when tethered with LexA, acts as a nucleation center for the transition from euchromatin to heterochromatin in an HDA-1 dependent fashion. Constitutive heterochromatin by contrast is largely HDA1 independent and depends on HDA-1 paralogs. RID is thus a dual function initiator of both RIP and the transition to heterochromatin.

Original language	English
Article number	gkaf263
Journal	Nucleic Acids Research
Volume	53
Issue number	6
Early online date	4 Apr 2025
DOIs	https://doi.org/10.1093/nar/gkaf263
Publication status	Published - 11 Apr 2025

Data Availability Statement

The complete DNA sequencing, 5mC methylation sequencing, and ChIP-seq data generated during this study are available in the National Center for Biotechnology Information Sequence Read Archive repository under study accession number PRJNA1165970. The mass spectrometry data have been deposited in PRIDE (https://www.ebi.ac.uk/pride/) under project PXD060025. Sequences of the R-L-R constructs, Sly1-1 and Sly1-1r, positions of duplication regions, and custom codes used in this study are deposited in https://github.com/jujushen/NcrassaRID and https://doi.org/10.5281/zenodo.15057073.

Acknowledgements

We thank Professor Chaoguang Tian at the Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, for the kind gift of the FGSC2489 strain, and Professor Qun He at the College of Biological Sciences, China Agricultural University, for the kind gift of the ku70RIP strain. The graphical abstract was created in BioRender. Zhen, H. 2025 https://BioRender.com/i28n107.

Funding

This work was funded by the National Natural Science Foundation of China (32270664 and 32170327), Natural Science Foundation of Jiangsu Province for Distinguished Young Scholars (BK20240064), Jiangsu Collaborative Innovation Center for Modern Crop Production, the National Key Research and Development Program of China (2023YFD2200102 and 2023YFD2200104), and the Fundamental Research Funds for the Central Universities (14380209). Funding to pay the Open Access publication charges for this article was provided by JISC OUP Read & Publish deal of which U Bath has signed up.

ASJC Scopus subject areas

Genetics

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title = "RID is required for both repeat-induced point mutation and nucleation of a novel transitional heterochromatic state for euchromatic repeats",

abstract = "To maintain genome integrity, repeat sequences are subject to heterochromatin inactivation and, in Neurospora, repeat-induced point mutation (RIP). The initiating factors behind both are poorly understood. We resolve the paradoxical observation that newly introduced Repeat-Linker-Repeat (R-L-R) constructs require RID alone for RIP, while genomic repeats are RIPed in the absence of RID, showing that eu- and hetero- chromatic repeats are handled differently, the latter additionally requiring DIM-2. The differences between mechanisms associated with older and newer duplicates caution against extrapolation from mechanisms inferred from model experimental systems. Additionally, while chromatin status affects RIP, we also show that RID, when tethered with LexA, acts as a nucleation center for the transition from euchromatin to heterochromatin in an HDA-1 dependent fashion. Constitutive heterochromatin by contrast is largely HDA1 independent and depends on HDA-1 paralogs. RID is thus a dual function initiator of both RIP and the transition to heterochromatin.",

author = "Zhen He and Nannan Wu and Ruonan Yao and Huawei Tan and Yingying Sun and Jingxuan Chen and Lan Xue and Xiaonan Chen and Sihai Yang and Hurst, \{Laurence D.\} and Long Wang and Ju Huang",

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AU - He, Zhen

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AU - Yao, Ruonan

AU - Tan, Huawei

AU - Sun, Yingying

AU - Chen, Jingxuan

AU - Xue, Lan

AU - Chen, Xiaonan

AU - Yang, Sihai

AU - Hurst, Laurence D.

AU - Wang, Long

AU - Huang, Ju

PY - 2025/4/11

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AB - To maintain genome integrity, repeat sequences are subject to heterochromatin inactivation and, in Neurospora, repeat-induced point mutation (RIP). The initiating factors behind both are poorly understood. We resolve the paradoxical observation that newly introduced Repeat-Linker-Repeat (R-L-R) constructs require RID alone for RIP, while genomic repeats are RIPed in the absence of RID, showing that eu- and hetero- chromatic repeats are handled differently, the latter additionally requiring DIM-2. The differences between mechanisms associated with older and newer duplicates caution against extrapolation from mechanisms inferred from model experimental systems. Additionally, while chromatin status affects RIP, we also show that RID, when tethered with LexA, acts as a nucleation center for the transition from euchromatin to heterochromatin in an HDA-1 dependent fashion. Constitutive heterochromatin by contrast is largely HDA1 independent and depends on HDA-1 paralogs. RID is thus a dual function initiator of both RIP and the transition to heterochromatin.

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RID is required for both repeat-induced point mutation and nucleation of a novel transitional heterochromatic state for euchromatic repeats

Abstract

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Acknowledgements

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