Sult1b1-KO Mouse

SULT1B1, a cytosolic sulfotransferase, is involved in sulfonation reactions, biotransforming small molecules into polar sulfate esters [3,4]. It plays a role in the biotransformation of endogenous substances like thyroid hormones and is also implicated in the metabolism of xenobiotics, activation of procarcinogens, and regulation of hormones [5,6]. Structurally, it contains key domains for substrate and PAPS binding [4,5].

In a study on histone modifications, SULT1B1 was found to be a histone sulfotransferase. It sulfates the tyrosine 99 residue of nascent histone H3 in the cytosol. The sulfated H3 is transported to the nucleus and deposited in gene promoter regions. This sulfation event is crucial as it enables the binding of PRMT1, which deposits H4R3me2a in chromatin. Disrupting H3Y99sulf reduces PRMT1 binding, H4R3me2a levels, and gene transcription, revealing a mechanism by which SULT1B1-mediated histone sulfation regulates gene transcription [1]. In addition, an allelic variant L145V of SULT1B1, specific to African Americans, shows altered kinetic properties, though no significant cancer-genotype correlation was observed [4]. Also, in colon cancer, SULT1B1 was identified as one of the genes associated with prognosis through machine-learning-based bioinformatics analysis [2].

In conclusion, SULT1B1 is important for histone-mediated gene regulation, and its allelic variants may have implications for specific populations. Its association with colon cancer prognosis suggests its potential as a biomarker. The functional studies on SULT1B1, especially those related to histone sulfation, contribute to our understanding of gene regulation mechanisms and disease-associated processes.

References:

1. Yu, Weixing, Zhou, Runxin, Li, Nan, Liu, Ke, Wang, Yugang. 2023. Histone tyrosine sulfation by SULT1B1 regulates H4R3me2a and gene transcription. In Nature chemical biology, 19, 855-864. doi:10.1038/s41589-023-01267-9. https://pubmed.ncbi.nlm.nih.gov/36805701/

2. Su, Ying, Tian, Xuecong, Gao, Rui, Li, Hongtao, Lv, Xiaoyi. 2022. Colon cancer diagnosis and staging classification based on machine learning and bioinformatics analysis. In Computers in biology and medicine, 145, 105409. doi:10.1016/j.compbiomed.2022.105409. https://pubmed.ncbi.nlm.nih.gov/35339846/

3. Tibbs, Zachary E, Falany, Charles N. 2016. An engineered heterodimeric model to investigate SULT1B1 dependence on intersubunit communication. In Biochemical pharmacology, 115, 123-33. doi:10.1016/j.bcp.2016.06.011. https://pubmed.ncbi.nlm.nih.gov/27338799/

4. Tibbs, Zachary E, Guidry, Amber L, Falany, Josie L, Kadlubar, Susan A, Falany, Charles N. 2017. A high frequency missense SULT1B1 allelic variant (L145V) selectively expressed in African descendants exhibits altered kinetic properties. In Xenobiotica; the fate of foreign compounds in biological systems, 48, 79-88. doi:10.1080/00498254.2017.1282646. https://pubmed.ncbi.nlm.nih.gov/28084139/

5. Sun, Huimiao, Lv, Liyuan, Chen, Caifang, He, Jing, Han, Qingxi. 2022. Genome-wide characterization of the cytosolic sulfotransferase 1B member 1 (SULT1B1) family and its expression responses to sulfide stress in the razor clam Sinonovacula constricta. In Gene, 856, 147136. doi:10.1016/j.gene.2022.147136. https://pubmed.ncbi.nlm.nih.gov/36572072/

6. Meinl, W, Glatt, H. . Structure and localization of the human SULT1B1 gene: neighborhood to SULT1E1 and a SULT1D pseudogene. In Biochemical and biophysical research communications, 288, 855-62. doi:. https://pubmed.ncbi.nlm.nih.gov/11688987/