Recombinant Human Activating transcription factor 7-interacting protein 1 (ATF7IP), Truncated

Activating transcription factor 7-interacting protein 1 (ATF7IP) is a multifunctional protein involved in various cellular processes. It has been shown to interact with methylated DNA-binding domain protein 1 (MBD1) and MBD1-containing chromatin-associated factor 1 (MCAF1), also known as ATFaassociated modulator (AM) [1]. ATF7IP is implicated in the maintenance of X chromosome inactivation (XCI) through its repressive context, where it mediates MBD1-dependent transcriptional silencing by recruiting and catalytically activating the histone H3K9 methyltransferase SETDB1 [2]. Furthermore, ATF7IP contains at least two functional binding surfaces for other proteins, such as SETDB1 and MBD1, and plays a role in efficient transcriptional silencing mediated by the SETDB1 complex [3][4]. It has also been identified as a transcriptional cofactor involved in histone gene expression and cellular senescence [5]. ATF7IP is recognized as a SETDB1-interacting protein and is essential for heterochromatin formation by the HUSH complex [6]. Additionally, ATF7IP has been reported to inhibit Il2 expression, regulating Th17 responses, and is an essential cofactor in SETDB1 enzymatic activity and nuclear localization [7]. Moreover, ATF7IP is involved in the regulation of SETDB1 nuclear localization and its enzymatic activity, as well as in increasing the levels of its ubiquitinated and more enzymatically active forms [8][9]. The protein also undergoes tri-methylation by G9a/GLP, recruiting the chromodomain protein MPP8, suggesting its involvement in gene regulation [10]. Interestingly, ATF7IP's methylation partially contributes to the function of the HUSH complex, as preventing K16 methylation led to a delay in HUSH complex silencing of a virally introduced transgene [11]. References:[1] L. Liu, K. Ishihara, T. Ichimura, N. Fujita, S. Hino, S. Tomitaet al., "Mcaf1/am is involved in sp1-mediated maintenance of cancer-associated telomerase activity", Journal of Biological Chemistry, vol. 284, no. 8, p. 5165-5174, 2009. https://doi.org/10.1074/jbc.m807098200[2] A. Minkovsky, A. Sahakyan, E. Rankin-Gee, G. Bonora, S. Patel, & K. Plath, "The mbd1-atf7ip-setdb1 pathway contributes to the maintenance of x chromosome inactivation", Epigenetics & Chromatin, vol. 7, no. 1, 2014. https://doi.org/10.1186/1756-8935-7-12[3] T. Tsusaka, K. Fukuda, C. Shimura, M. Kato, & Y. Shinkai, "The fibronectin type-iii (fniii) domain of atf7ip contributes to efficient transcriptional silencing mediated by the setdb1 complex", Epigenetics & Chromatin, vol. 13, no. 1, 2020. https://doi.org/10.1186/s13072-020-00374-4[4] Y. Li, B. Sun, L. Xu, L. Chen, & W. Ou, "The updating of biological functions of methyltransferase setdb1 and its relevance in lung cancer and mesothelioma", International Journal of Molecular Sciences, vol. 22, no. 14, p. 7416, 2021. https://doi.org/10.3390/ijms22147416[5] N. Sasai, N. Saitoh, H. Saitoh, & M. Nakao, "The transcriptional cofactor mcaf1/atf7ip is involved in histone gene expression and cellular senescence", Plos One, vol. 8, no. 7, p. e68478, 2013. https://doi.org/10.1371/journal.pone.0068478[6] R. Timms, I. Tchasovnikarova, R. Antrobus, G. Dougan, & P. Lehner, "Atf7ip-mediated stabilization of the histone methyltransferase setdb1 is essential for heterochromatin formation by the hush complex", Cell Reports, vol. 17, no. 3, p. 653-659, 2016. https://doi.org/10.1016/j.celrep.2016.09.050[7] J. Sin, C. Zuckerman, J. Cortez, W. Eckalbar, D. Erle, M. Andersonet al., "The epigenetic regulator atf7ip inhibits il2 expression, regulating th17 responses", The Journal of Experimental Medicine, vol. 216, no. 9, p. 2024-2037, 2019. https://doi.org/10.1084/jem.20182316[8] T. Tsusaka, C. Shimura, & Y. Shinkai, "Atf7ip regulates setdb1 nuclear localization and increases its ubiquitination", Embo Reports, vol. 20, no. 12, 2019. https://doi.org/10.15252/embr.201948297[9] Y. Shinkai, T. Tsusaka, K. Fukuda, C. Shimura, & M. Kato, "The fibronectin type-iii (fniii) domain of atf7ip contributes to efficient transcriptional silencing mediated by the setdb1 complex ",, 2020. https://doi.org/10.21203/rs.3.rs-44959/v2[10] T. Tsusaka, M. Kikuchi, T. Shimazu, T. Suzuki, Y. Sohtome, M. Akakabeet al., "Tri-methylation of atf7ip by g9a/glp recruits the chromodomain protein mpp8", Epigenetics & Chromatin, vol. 11, no. 1, 2018. https://doi.org/10.1186/s13072-018-0231-z[11] E. Cornett, L. Ferry, P. Defossez, & S. Rothbart, "Lysine methylation regulators moonlighting outside the epigenome", Molecular Cell, vol. 75, no. 6, p. 1092-1101, 2019. https://doi.org/10.1016/j.molcel.2019.08.026