Kat7-KO Mouse

KAT7, also known as HBO1 (histone acetyltransferase binding to ORC1) or MYST2, is a histone acetyltransferase. It plays a crucial role in histone H3 lysine 14 acetylation (H3K14Ac), which is involved in regulating gene expression. KAT7 is associated with multiple biological pathways, including those related to cell senescence, MTORC1 activity, hematopoietic stem cell function, and various cancer-related processes [1,2,3]. Genetic models, especially gene knockout (KO) and conditional knockout (CKO) mouse models, are valuable tools for studying KAT7.

In KO mouse models, inactivation of KAT7 in human mesenchymal precursor cells (hMPCs) alleviated cellular senescence, as it decreased H3K14Ac, repressed p15INK4b transcription [1]. In hematopoietic stem cells, Hbo1 (KAT7)-null mice showed hematopoietic failure due to rapid loss of progenitors and abnormal recruitment of quiescent hematopoietic stem cells into the cell cycle [3]. In cancer research, silencing KAT7 in head and neck squamous carcinoma (HNSCC) inhibited the Warburg effect, reducing cell proliferation, invasion, and metastasis [4]. In breast cancer, KAT7 silencing suppressed radioresistance in vitro by down-regulating the PI3K/AKT signaling pathway [5].

In conclusion, KAT7 is essential for regulating histone acetylation and gene expression. Through KO/CKO mouse models, its role in promoting cellular senescence, regulating hematopoietic stem cell function, and driving cancer progression has been revealed. These findings highlight the potential of targeting KAT7 in developing interventions for aging-related diseases and various cancers.

References:

1. Wang, Wei, Zheng, Yuxuan, Sun, Shuhui, Tang, Fuchou, Liu, Guang-Hui. . A genome-wide CRISPR-based screen identifies KAT7 as a driver of cellular senescence. In Science translational medicine, 13, . doi:10.1126/scitranslmed.abd2655. https://pubmed.ncbi.nlm.nih.gov/33408182/

2. Yan, Guokai, Li, Xiuzhi, Zheng, Zilong, Zhong, Qing, Yan, Xianghua. 2022. KAT7-mediated CANX (calnexin) crotonylation regulates leucine-stimulated MTORC1 activity. In Autophagy, 18, 2799-2816. doi:10.1080/15548627.2022.2047481. https://pubmed.ncbi.nlm.nih.gov/35266843/

3. Yang, Yuqing, Kueh, Andrew J, Grant, Zoe L, Voss, Anne K, Thomas, Tim. . The histone lysine acetyltransferase HBO1 (KAT7) regulates hematopoietic stem cell quiescence and self-renewal. In Blood, 139, 845-858. doi:10.1182/blood.2021013954. https://pubmed.ncbi.nlm.nih.gov/34724565/

4. Lu, Ying, Wang, Yong, Zhang, Leilei, Du, Yimeng, Li, Qihong. 2024. KAT7 enhances the proliferation and metastasis of head and neck squamous carcinoma by promoting the acetylation level of LDHA. In Cancer letters, 590, 216869. doi:10.1016/j.canlet.2024.216869. https://pubmed.ncbi.nlm.nih.gov/38593918/

5. Ma, Yan, Chen, Xiaohua, Ding, Ting, Tang, Jianming, Wang, Xiaohu. . KAT7 promotes radioresistance through upregulating PI3K/AKT signaling in breast cancer. In Journal of radiation research, 64, 448-456. doi:10.1093/jrr/rrac107. https://pubmed.ncbi.nlm.nih.gov/36724120/