Atf7ip-flox Mouse
一般名
Atf7ip-flox
製品ID
S-CKO-11722
背景情報
C57BL/6JCya
系統ID
CKOCMP-54343-Atf7ip-B6J-VA
状況
このマウス系統を論文で使用する場合は、「Atf7ip-flox Mouse（カタログ番号S-CKO-11722）はサイアジェンから購入しました。」と引用してください。
製品タイプ
年齢
遺伝子型
性別
数量
標準的な配送方法では、少なくとも3匹のヘテロ接合体キャリアを保証しています。ホモ接合体キャリアや指定された性別の個体の繁殖サービスも利用可能です。
基本情報
系統名
Atf7ip-flox
系統ID
CKOCMP-54343-Atf7ip-B6J-VA
遺伝子名
製品ID
S-CKO-11722
遺伝子別名
AM, Mcaf1, 2610204M12Rik, 5830415B17Rik
遺伝子別名
C57BL/6JCya
NCBI ID
修正
Conditional knockout
染色体
Chr 6
表現型
アプリケーション
--
さらに
系統詳細
EnsemblトランスクリプトID
ENSMUST00000032335
NCBIトランスクリプトID
NM_019426
ターゲット領域
Exon 2
有効領域の大きさ
~2.2 kb
遺伝子研究の概要
Atf7ip, the activating transcription factor 7 interacting protein, is an epigenetic regulator. It interacts with Setdb1, a lysine methyltransferase responsible for histone H3 lysine 9 (H3K9) methylation. Together, they play a crucial role in various biological processes through H3K9me3 modification and chromatin remodeling, influencing gene expression and cell differentiation [1,2,3,4,5,6,7,8].
In zebrafish, Atf7ip-deficient mutants show excessive myeloid differentiation with impaired hematopoietic stem and progenitor cell (HSPC) expansion, leading to a decline in T cells and erythroid lineage. Atf7ip regulates hematopoiesis via Setdb1-mediated H3K9me3 modification in hematopoietic regulatory genes, preventing premature myeloid differentiation. Also, loss of Atf7ip derepresses retrotransposons, triggering viral sensor signaling and stress-driven myelopoiesis and inflammation. In human leukemic cells, ATF7IP depletion represses cell growth and induces myeloid differentiation with retrotransposon-triggered inflammation [1].
In mice, T cell-specific deletion of ATF7ip enhances Il7r and Il2 expression in CD8+ T cells, leading to enhanced effector and memory responses, as ATF7ip represses these genes through H3K9me3 deposition at relevant loci [3]. Mice with T cell-specific deletion of Atf7ip have impaired Th17 differentiation due to aberrant IL-2 overproduction, as Atf7ip inhibits Il2 gene expression through H3K9me3 deposition in the Il2-Il21 intergenic region [5]. Disrupting Atf7ip in tumor cells restores tumor antigen expression, augments tumor immunogenicity, and leads to increased T-cell infiltration and tumor rejection [6].
In osteoblasts, Atf7ip inhibits differentiation. Atf7ip-deficient mice (Oc-Cre;Atf7ipf/f) show more bone formation. Atf7ip contributes to Setdb1's nucleus localization in osteoblasts and negatively regulates Sp7 expression [2].
In summary, Atf7ip, mainly through its interaction with Setdb1 and H3K9me3-related epigenetic regulation, is essential in hematopoiesis, immune cell function, and osteoblast differentiation. Gene-knockout mouse models have revealed its role in hematological malignancies, autoimmune diseases, cancer immunology, and bone-related conditions, providing potential targets for intervention in these disease areas.
References：
1. Wu, Jiaxin, Li, Juan, Chen, Kang, Xie, Peng, Zhong, Tao P. 2022. Atf7ip and Setdb1 interaction orchestrates the hematopoietic stem and progenitor cell state with diverse lineage differentiation. In Proceedings of the National Academy of Sciences of the United States of America, 120, e2209062120. doi:10.1073/pnas.2209062120. https://pubmed.ncbi.nlm.nih.gov/36577070/
2. Hu, Guoqin, Shi, Xian, Qu, Xiuxia, Liu, Huanliang, Wu, Yu. 2023. Atf7ip Inhibits Osteoblast Differentiation via Negative Regulation of the Sp7 Transcription Factor. In International journal of molecular sciences, 24, . doi:10.3390/ijms24054305. https://pubmed.ncbi.nlm.nih.gov/36901736/
3. Sin, Jun Hyung, Kashyap, Sujit, Acenas, Dante, Matloubian, Mehrdad, Waterfield, Michael R. 2022. ATF7ip Targets Transposable Elements for H3K9me3 Deposition to Modify CD8+ T Cell Effector and Memory Responses. In Journal of immunology (Baltimore, Md. : 1950), 208, 1155-1169. doi:10.4049/jimmunol.2100996. https://pubmed.ncbi.nlm.nih.gov/35110421/
4. Tsusaka, Takeshi, Shimura, Chikako, Shinkai, Yoichi. 2019. ATF7IP regulates SETDB1 nuclear localization and increases its ubiquitination. In EMBO reports, 20, e48297. doi:10.15252/embr.201948297. https://pubmed.ncbi.nlm.nih.gov/31576654/
5. Sin, Jun Hyung, Zuckerman, Cassandra, Cortez, Jessica T, Anderson, Mark S, Waterfield, Michael R. 2019. The epigenetic regulator ATF7ip inhibits Il2 expression, regulating Th17 responses. In The Journal of experimental medicine, 216, 2024-2037. doi:10.1084/jem.20182316. https://pubmed.ncbi.nlm.nih.gov/31217192/
6. Hu, Hai, Khodadadi-Jamayran, Alireza, Dolgalev, Igor, Li, Fei, Wong, Kwok-Kin. 2021. Targeting the Atf7ip-Setdb1 Complex Augments Antitumor Immunity by Boosting Tumor Immunogenicity. In Cancer immunology research, 9, 1298-1315. doi:10.1158/2326-6066.CIR-21-0543. https://pubmed.ncbi.nlm.nih.gov/34462284/
7. Kariapper, Leena, Marathe, Ila A, Niesman, Ashley B, Wysocki, Vicki H, Worden, Evan J. 2024. Setdb1 and Atf7IP form a hetero-trimeric complex that blocks Setdb1 nuclear export. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.12.23.630145. https://pubmed.ncbi.nlm.nih.gov/39764026/
8. Timms, Richard T, Tchasovnikarova, Iva A, Antrobus, Robin, Dougan, Gordon, Lehner, Paul J. . ATF7IP-Mediated Stabilization of the Histone Methyltransferase SETDB1 Is Essential for Heterochromatin Formation by the HUSH Complex. In Cell reports, 17, 653-659. doi:10.1016/j.celrep.2016.09.050. https://pubmed.ncbi.nlm.nih.gov/27732843/
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