| 1. |
Sui Jianan, Chen Jiazi, Chen Yuehui, Iwamori Naoki, Sun Jin, ProSE-Pero: Peroxisomal Protein Localization Identification Model Based on Self-Supervised Multi-Task Language Pre-Training Model, Front Biosci (Landmark Ed), 10.31083/j.fbl2812322, 28, 12, 322, 2023.12. |
| 2. |
Sui Jianan, Chen Jiazi, Chen Yuehui, Iwamori Naoki, Sun Jin, Identification of plant vacuole proteins by using graph neural network and contact maps, BMC Bioinformatics, 10.1186/s12859-023-05475-x, 24, 1, 357, 2023.09. |
| 3. |
Imai Hiroyuki, Iwamori Naoki, Iwamori Tokuko, Matsuya Sumito, Kano Kiyoshi, Kusakabe Ken Takeshi, Verification of the efficacy of deciduae for determining the genetic type of mouse embryos, Anat Histol Embryol, 10.1111/ahe.12976, 53, 1, e12976, 2024.01. |
| 4. |
Sultana Tasrin, Iwamori Tokuko, Iwamori Naoki, TSNAXIP1 is required for sperm head formation and male fertility., Reproductive Medicine and Biology, 10.1002/rmb2.12520, 22, 1, e12520, 2023.06, Purpose: TRANSLIN (TSN) and its binding partner TSNAX have been reported to contribute to a wide spectrum of biological activities including spermatogenesis. TSN accompanies specific mRNA transport in male germ cells through intercellular bridges. A testis-expressed protein TSNAXIP1 was reported to interact with TSNAX. However the role of TSNAXIP1 in spermatogenesis remained unclear. This study aimed to elucidate the role of TSNAXIP1 in spermatogenesis and male fertility in mice.
Methods: TSNAXIP1 knockout (KO) mice were generated using the CRISPR-Cas9 system. The fertility, spermatogenesis, and sperm of TSNAXIP1 KO males were analyzed.
Results: TSNAXIP1, and especially its domains, are highly conserved between mouse and human. Tsnaxip1 was expressed in testis, but not in ovary. TSNAXIP1 KO mice were generated, and TSNAXIP1 KO males were found to be sub-fertile with smaller testis and lower sperm count. Although no overt abnormalities were observed during spermatogenesis, lack of TSNAXIP1 induced sperm head malformation, resulting in a unique flower-shaped sperm head. Moreover, abnormal anchorage of the sperm neck was frequently observed in TSNAXIP1 null sperm.
Conclusion: A testis-expressed gene TSNAXIP1 has important roles in sperm head morphogenesis and male fertility. Moreover, TSNAXIP1 could be a causative gene for human infertility.. |
| 5. |
Tominaga Kaoru、Sakashita Eiji、Kasashima Katsumi、Kuroiwa Kenji、Nagao Yasumitsu、Iwamori Naoki、Endo Hitoshi, Tip60/KAT5 Histone Acetyltransferase Is Required for Maintenance and Neurogenesis of Embryonic Neural Stem Cells., International Journal of Molecular Sciences, 10.3390/ijms24032113, 24, 3, 2113, 2023.01, Epigenetic regulation via epigenetic factors in collaboration with tissue-specific transcription factors is curtail for establishing functional organ systems during development. Brain development is tightly regulated by epigenetic factors, which are coordinately activated or inactivated during processes, and their dysregulation is linked to brain abnormalities and intellectual disability. However, the precise mechanism of epigenetic regulation in brain development and neurogenesis remains largely unknown. Here, we show that Tip60/KAT5 deletion in neural stem/progenitor cells (NSCs) in mice results in multiple abnormalities of brain development. Tip60-deficient embryonic brain led to microcephaly, and proliferating cells in the developing brain were reduced by Tip60 deficiency. In addition, neural differentiation and neuronal migration were severely affected in Tip60-deficient brains. Following neurogenesis in developing brains, gliogenesis started from the earlier stage of development in Tip60-deficient brains, indicating that Tip60 is involved in switching from neurogenesis to gliogenesis during brain development. It was also confirmed in vitro that poor neurosphere formation, proliferation defects, neural differentiation defects, and accelerated astrocytic differentiation in mutant NSCs are derived from Tip60-deficient embryonic brains. This study uncovers the critical role of Tip60 in brain development and NSC maintenance and function in vivo and in vitro.. |
| 6. |
Yang Bin、Bao Wenzheng、Wang Jinglong、Chen Baitong、Iwamori Naoki、Chen Jiazi、Chen Yuehui, Disease-related compound identification based on deeping learning method., Scientific Reports, 10.1038/s41598-022-24385-1, 12, 1, 20594, 2022.11, Acute lung injury (ALI) is a serious respiratory disease, which can lead to acute respiratory failure or death. It is closely related to the pathogenesis of New Coronavirus pneumonia (COVID-19). Many researches showed that traditional Chinese medicine (TCM) had a good effect on its intervention, and network pharmacology could play a very important role. In order to construct "disease-gene-target-drug" interaction network more accurately, deep learning algorithm is utilized in this paper. Two ALI-related target genes (REAL and SATA3) are considered, and the active and inactive compounds of the two corresponding target genes are collected as training data, respectively. Molecular descriptors and molecular fingerprints are utilized to characterize each compound. Forest graph embedded deep feed forward network (forgeNet) is proposed to train. The experimental results show that forgeNet performs better than support vector machines (SVM), random forest (RF), logical regression (LR), Naive Bayes (NB), XGBoost, LightGBM and gcForest. forgeNet could identify 19 compounds in Erhuang decoction (EhD) and Dexamethasone (DXMS) more accurately.. |
| 7. |
Ogata H, Tsukamoto M, Yamashita K, Iwamori T, Takahashi H, Kaneko T, Iwamori N, Inai T, Iida H., Effects of Calyculin a on the Motility and Protein Phosphorylation in Frozen-Thawed Bull Spermatozoa, Zoolog Sci, 10.2108/zs210046, 38, 6, 531-543, 2021.12. |
| 8. |
Wang Y, Iwamori T, Kaneko T, Iida H, Iwamori N., Comparative distributions of RSBN1 and methylated histone H4 Lysine 20 in the mouse spermatogenesis, PLOS One, 10.1371/journal.pone.0253897, 16, 6, e0253897, 2021.06, During spermatogenesis, nuclear architecture of male germ cells is dynamically changed and epigenetic modifications, in particular methylation of histones, highly contribute to its regulation as well as differentiation of male germ cells. Although several methyltransferases and demethylases for histone H3 are involved in the regulation of spermatogenesis, roles of either histone H4 lysine 20 (H4K20) methyltransferases or H4K20 demethylases during spermatogenesis still remain to be elucidated. Recently, RSBN1 which is a testis-specific gene expressed in round spermatids was identified as a demethylase for dimethyl H4K20. In this study, therefore, we confirm the demethylase function of RSBN1 and compare distributions between RSBN1 and methylated H4K20 in the seminiferous tubules. Unlike previous report, expression analyses for RSBN1 reveal that RSBN1 is not a testis-specific gene and is expressed not only in round spermatids but also in elongated spermatids. In addition, RSBN1 can demethylate not only dimethyl H4K20 but also trimethyl H4K20 and could convert both dimethyl H4K20 and trimethyl H4K20 into monomethyl H4K20. When distribution pattern of RSBN1 in the seminiferous tubule is compared to that of methylated H4K20, both dimethyl H4K20 and trimethyl H4K20 but not monomethyl H4K20 are disappeared from RSBN1 positive germ cells, suggesting that testis-specific distribution patterns of methylated H4K20 might be constructed by RSBN1. Thus, novel expression and function of RSBN1 could be useful to comprehend epigenetic regulation during spermatogenesis.. |
| 9. |
Kaneko T, Toh S, Mochida I, Iwamori N, Inai T, and IIda H, Identification of TMCO2 as an acrosome-associated protein during rat spermiogenesis, MOLECULAR REPRODUCTION AND DEVELOPMENT, 10.1002/mrd.23396, 87, 7, 808-818, 2020.07. |
| 10. |
Iwamori T, Iwamori N, Matsumoto M, Imai H, Ono E, Novel localizations and interactions of intercellular bridge proteins revealed by proteomic profiling., Biology of Reproduction, 10.1093/biolre/ioaa017, 102, 5, 1134-1144, 2020.04. |
| 11. |
Byun S, Seok S, Kim YC, Zhang Y, Yau P, Iwamori N, Xu HE, Ma J, Kemper B, Kemper JK, Fasting-induced FGF21 signaling activates hepatic autophagy and lipid degradation via JMJD3 histone demethylase, NATURE COMMUNICATIONS, 10.1038/s41467-020-14384-z, 11, 1, 807, 2020.02, Autophagy is essential for cellular survival and energy homeostasis under nutrient deprivation. Despite the emerging importance of nuclear events in autophagy regulation, epigenetic control of autophagy gene transcription remains unclear. Here, we report fasting-induced Fibroblast Growth Factor-21 (FGF21) signaling activates hepatic autophagy and lipid degradation via Jumonji-D3 (JMJD3/KDM6B) histone demethylase. Upon FGF21 signaling, JMJD3 epigenetically upregulates global autophagy-network genes, including Tfeb, Atg7, Atgl, and Fgf21, through demethylation of histone H3K27-me3, resulting in autophagy-mediated lipid degradation. Mechanistically, phosphorylation of JMJD3 at Thr-1044 by FGF21 signal-activated PKA increases its nuclear localization and interaction with the nuclear receptor PPARα to transcriptionally activate autophagy. Administration of FGF21 in obese mice improves defective autophagy and hepatosteatosis in a JMJD3-dependent manner. Remarkably, in non-alcoholic fatty liver disease patients, hepatic expression of JMJD3, ATG7, LC3, and ULK1 is substantially decreased. These findings demonstrate that FGF21-JMJD3 signaling epigenetically links nutrient deprivation with hepatic autophagy and lipid degradation in mammals.. |
| 12. |
Mallaney C, Ostrander EL, Celik H, Kramer AC, Martens A, Kothari A, Koh WK, Haussler E, Iwamori N, Gontarz P, Zhang B, Challen GA, Kdm6b requires context-dependent hematopoietic stem cell self-renewal and leukemogenesis., Leukemia, 10.1038/s41375-019-0462-4, 33, 10, 2506-2521, 2019.10. |
| 13. |
Takane Kaneko, Taisuke Minohara, Sakurako Shima, Kaori Yoshida, Atsuko Fukuda, Naoki Iwamori, Tetsuichiro Inai, Hiroshi Iida, A membrane protein, TMCO5A, has a close relationship with manchette microtubules in rat spermatids during spermiogenesis, MOLECULAR REPRODUCTION AND DEVELOPMENT, 10.1002/mrd.23108, 86, 3, 330-341, 2019.03. |
| 14. |
Seok S, Kim YC, Byun S, Choi S, Xiao Z, Iwamori N, Zhang Y, Wang C, Ma J, Ge K, Kemper B, Kemper JK, Fasting-induced JMJD3 histone demethylase epigenetically activates mitochondrial fatty acid b-oxidation., Journal of Clinical Investigation, 10.1172/JCI97736., 128, 7, 3144-3159, 2018.07, Jumonji D3 (JMJD3) histone demethylase epigenetically regulates development and differentiation, immunity, and tumorigenesis by demethylating a gene repression histone mark, H3K27-me3, but a role for JMJD3 in metabolic regulation has not been described. SIRT1 deacetylase maintains energy balance during fasting by directly activating both hepatic gluconeogenic and mitochondrial fatty acid β-oxidation genes, but the underlying epigenetic and gene-specific mechanisms remain unclear. In this study, JMJD3 was identified unexpectedly as a gene-specific transcriptional partner of SIRT1 and epigenetically activated mitochondrial β-oxidation, but not gluconeogenic, genes during fasting. Mechanistically, JMJD3, together with SIRT1 and the nuclear receptor PPARα, formed a positive autoregulatory loop upon fasting-activated PKA signaling and epigenetically activated β-oxidation-promoting genes, including Fgf21, Cpt1a, and Mcad. Liver-specific downregulation of JMJD3 resulted in intrinsic defects in β-oxidation, which contributed to hepatosteatosis as well as glucose and insulin intolerance. Remarkably, the lipid-lowering effects by JMJD3 or SIRT1 in diet-induced obese mice were mutually interdependent. JMJD3 histone demethylase may serve as an epigenetic drug target for obesity, hepatosteatosis, and type 2 diabetes that allows selective lowering of lipid levels without increasing glucose levels.. |
| 15. |
Herédi J, Berkó AM, Jankovics F, Iwamori T, Iwamori N, Ono E, Horváth S, Kis Z, Toldi J, Vécsei L, Gellért L, Astrocytic and neuronal localization of kynurenine aminotransferase-2 in the adult mouse brain, BRAIN STRUCTURE & FUNCTION, 10.1007/s00429-016-1299-5, 222, 4, 1663-1672, 2017.05. |
| 16. |
Tokuko Iwamori, Naoki IWAMORI, Masaki Matsumoto, Etsuro Ono, Martin M. Matzuk, Identification of KIAA1210 as a novel X-chromosome-linked protein that localizes to the acrosome and associates with the ectoplasmic specialization in testes, BIOLOGY OF REPRODUCTION, 10.1095/biolreprod.116.145458, 96, 2, 469-477, 2017.02. |
| 17. |
Naoki IWAMORI, Kaoru Tominaga, Sato Tetsuya, Kevin Riehle, Tokuko Iwamori, Yasuyuki Ohkawa, Cristian Coarfa, Etsuro Ono, Martin M. Matzuk, MRG15 is required for pre-mRNA splicing and spermatogenesis, PNAS, 10.1073/pnas.1611995113, 113, 37, E5408-E5415, 2016.09, Splicing can be epigenetically regulated and involved in cellular differentiation in somatic cells, but the interplay of epigenetic factors and the splicing machinery during spermatogenesis re- mains unclear. To study these interactions in vivo, we generated a germline deletion of MORF-related gene on chromosome 15 (MRG15), a multifunctional chromatin organizer that binds to methylated histone H3 lysine 36 (H3K36) in introns of transcriptionally active genes and has been implicated in regulation of histone acetyla- tion, homology-directed DNA repair, and alternative splicing in somatic cells. Conditional KO (cKO) males lacking MRG15 in the germline are sterile secondary to spermatogenic arrest at the round spermatid stage. There were no significant alterations in meiotic division and histone acetylation. Specific mRNA sequences disappeared from 66 germ cell-expressed genes in the absence of MRG15, and specific intronic sequences were retained in mRNAs of 4 genes in the MRG15 cKO testes. In particular, introns were retained in mRNAs encoding the transition proteins that replace histones during sperm chromatin condensation. In round spermatids, MRG15 colocalizes with splicing factors PTBP1 and PTBP2 at H3K36me3 sites between the exons and single intron of transition nuclear protein 2 (Tnp2). Thus, our results reveal that MRG15 is essential for pre- mRNA splicing during spermatogenesis and that epigenetic regula- tion of pre-mRNA splicing by histone modification could be useful to understand not only spermatogenesis but also, epigenetic disor- ders underlying male infertile patients.. |
| 18. |
Fujimoto Y, K. Ozaki, N. IWAMORI, Etsuro Ono, Accumulation of a soluble form of human nectin-2 is required for exerting the resistance against herpes simplex virus type 2 infection in transfected cells, Acta Virologica, 60, 1, 41-48, 2016.03. |
| 19. |
D. Varga, J. Heredi, Z. Kanvasi, M. Ruszka, Z. Kis, E. Ono, N. IWAMORI, T. Iwamori, H. Takakuwa, L. Vecsei, J. Toldi, L. Gellert, Systemic L-Kynurenine sulfate administration disrupts object recognition memory, alters open field behavior and decreases c-Fos immunopositivity in C57BL/6 mice, FRONTIERS IN BEHAVIORAL NEUROSCIENCE, 10.3389/fnbeh.2015.00157, 9, 14-24, 2015.06. |
| 20. |
Dae Hwi Park, Sung Jun Hong, Ryan D. Salinas, Siyuan John Liu, Shawn W. Sun, Jacopo Sgualdino, Giuseppe Testa, Martin M. Matzuk, N. IWAMORI, Daniel A. Lim, Activation of Neuronal Gene Expression by the JMJD3 Demethylase Is Required for Postnatal and Adult Brain Neurogenesis, CELL REPORTS, 10.1016/j.celrep.2014.07.060, 8, 5, 1290-1299, 2014.09. |
| 21. |
K. KOCSIS, L. KNAPP, L. GELLERT, G. OLAH, ZS. KIS, H. TAKAKUWA, N. IWAMORI, E. ONO, J. TOLDI, T. FARKAS, Acetyl-l-carnitine normalizes the impaired long-term potentiation and spine density in a rat model of global ischemia., Neuroscience, 10.1016/j.neuroscience.2014.03.055, 269, 265-272, 2014.06. |
| 22. |
Yukiko Tomioka, Masami Morimatsu, Satoshi Taharaguchi, Sayo Yamamoto, Haruka Suyama, Kinuyo Ozaki, Naoki Iwamori, Etsuro Ono, Abnormal spermatogenesis and reduced fertility in transgenic mice expressing the immediate-early protein IE180 of pseudorabies virus, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 10.1016/j.bbrc.2013.09.125, 440, 4, 683-688, 2013.11. |
| 23. |
Naoki Iwamori, Tokuko Iwamori, Martin M. Matzuk, H3K27 demethylase, JMJD3, regulates fragmentation of spermatogonial cysts., PLoS ONE, 10.1371/journal.pone.0072689, 8, 8, e72689, 2013.08. |
| 24. |
Lee SJ, Huynh TV, Lee YS, Sebald SM, Wilcox-Adelman SA, Naoki Iwamori, Lepper C, Matzuk MM, Fan CM, Role of satellite cells versus myofibers in muscle hypertrophy induced by inhibition of the myostatin/activin signaling pathway, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 10.1073/pnas.1206410109, 109, 35, E2353-E2360, 2012.08. |
| 25. |
Iwamori N, Iwamori T, Matzuk MM, Characterization of spermatogonial stem cells lacking intercellular bridges and genetic replacement of a mutation in spermatogonial stem cells., PLoS One, 7, 6, e38914, 2012.06. |
| 26. |
Tokuko Iwamori, Yi-Nan Lin, Lang Ma, Naoki Iwamori, Martin M Matzuk, Identification and Characterization of RBM44 as a Novel Intercellular Bridge Protein, PLOS ONE, 10.1371/journal.pone.0017066, 6, 2, e17066, 2011.02. |
| 27. |
Iwamori N, Zhao M, Meistrich ML, Matzuk MM, The testis-enriched histone demethylase, JMJD2D, regulates methylation of histone H3 lysine 9 during spermatogenesis but is dispensable for fertility. , Biol. Reprod, 84, 6, 1225-1234, 2011.06. |
| 28. |
Iwamori T, Iwamori N, Ma L, Edson MA, Greenbaum MP, Matzuk MM, TEX14 interacts with CEP55 to block cell abscission., Mol Cell Biol, 30, 9, 2280-2292, 2010.05. |
| 29. |
Greenbaum MP, Iwamori N, Agno JE, Matzuk MM, Mouse TEX14 is required for embryonic germ cell intercellular bridges but not female fertility., Biol. Reprod, 80, 3, 449-457, 2009.03. |
| 30. |
Iwamori N, Naito K, Sugiura K, Tojo H, Preimplantation-embryo-specific cell cycle regulation is attributed to the low expression level of retinoblastoma protein. , FEBS Lett, 526, 1-3, 119-123, 2002.08. |
| 31. |
Iwamori N, Naito K, Sugiura K, Kagii H, Yamashita M, Ohashi S, Goto S, Yamanouch K, Tojo H, Phosphorylation of mitogen-activated protein kinase cascade during early embryo development in the mouse. , Reprod. Fertil. Dev, 12, 3-4, 209-214, 2000.03. |
