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Int J Biol Sci 2024; 20(2):554-568. doi:10.7150/ijbs.89958 This issue Cite

Research Paper

Protein arginine methyltransferase 1 is required for the maintenance of adult small intestinal and colonic epithelial cell homeostasis

Zhaoyi Peng^1,2†, Lingyu Bao^1,2†, Bingyin Shi^1✉, Yun-Bo Shi^2✉

1. Department of Endocrinology, The First Affiliated Hospital of Xi'an JiaoTong University, No. 277, West Yanta Road, Xi'an, Shaanxi 710061, P.R. China.
2. Section on Molecular Morphogenesis, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, MD, USA.
^†Zhaoyi Peng and Lingyu Bao contributed equally to this work.

✉ Corresponding authors: Yun-Bo Shi, Shinih.gov; Bingyin Shi, shibingycom.

Abstract

The vertebrate adult intestinal epithelium has a high self-renewal rate driven by intestinal stem cells (ISCs) in the crypts, which play central roles in maintaining intestinal integrity and homeostasis. However, the underlying mechanisms remain elusive. Here we showed that protein arginine methyltransferase 1 (PRMT1), a major arginine methyltransferase that can also function as a transcription co-activator, was highly expressed in the proliferating cells of adult mouse intestinal crypts. Intestinal epithelium-specific knockout of PRMT1, which ablates PRMT1 gene starting during embryogenesis, caused distinct, region-specific effects on small intestine and colon: increasing and decreasing the goblet cell number in the small intestinal and colonic crypts, respectively, leading to elongation of the crypts in small intestine but not colon, while increasing crypt cell proliferation in both regions. We further generated a tamoxifen-inducible intestinal epithelium-specific PRMT1 knockout mouse model and found that tamoxifen-induced knockout of PRMT1 in the adult mice resulted in the same region-specific intestinal phenotypes. Thus, our studies have for the first time revealed that the epigenetic enzyme PRMT1 has distinct, region-specific roles in the maintenance of intestinal epithelial architecture and homeostasis, although PRMT1 may influence intestinal development.

Keywords: Epithelial homeostasis, Arginine methylation, methyltransferase, Intestine, Self-renewal, Stem cell

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