Article
Biology
Ai Vu Hong, Nathalie Bourg, Peggy Sanatine, Jerome Poupiot, Karine Charton, Evelyne Gicquel, Emmanuelle Massourides, Marco Spinazzi, Isabelle Richard, David Israeli
Summary: Duchenne muscular dystrophy (DMD) is characterized by up-regulation of Dlk1-Dio3 clustered miRNAs (DD-miRNAs) in regenerating myofibers and serum, leading to dysregulation of mitochondrial metabolism and oxidative phosphorylation. Overexpression of DD-miRNAs in mouse muscle showed similar changes to naturally occurring up-regulated DD-miRNAs in DMD, suggesting their role as mediators of dystrophic changes and targeting mitochondrial dysfunction.
LIFE SCIENCE ALLIANCE
(2022)
Article
Cell Biology
Junliang Li, Dawei Yu, Jing Wang, Chongyang Li, Qingwei Wang, Weihua Du, Shanjiang Zhao, Yunwei Pang, Haisheng Hao, Xueming Zhao, Huabin Zhu, Shijie Li, Huiying Zou
Summary: This study investigates the imprinting status and methylation regulation of the DLK1-DIO3 region in wild-type and cloned neonatal pigs. The results reveal the abnormal imprinting and hypermethylation in the DLK1-DIO3 region in cloned pigs, providing a theoretical basis for improving cloning efficiency by gene editing to correct abnormal imprinting.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Victor D. Martinez, Adam P. Sage, Brenda C. Minatel, Erin A. Marshall, E. Magda Price, Daiana D. Becker-Santos, Wendy P. Robinson, Wan L. Lam
Summary: The study reveals that 297 piRNAs are preferentially expressed in the human placenta, with some being expressed at higher levels compared to testes samples. The majority of placental piRNAs originate from a single locus, distinct from canonical cluster locations associated with transposable element silencing. Additionally, 15 of the highest-expressed placental piRNAs map to the DLK1-DIO3 locus, suggesting a link to placental biology.
SCIENTIFIC REPORTS
(2021)
Article
Genetics & Heredity
Natalia Baulina, Ivan Kiselev, Maxim Kozin, Anastasia Kabaeva, Alexey Boyko, Olga Favorova
Summary: The role of miRNAs in the development of multiple sclerosis has been widely studied. This study investigated the expression of miRNA genes from the DLK1-DIO3 locus in RRMS patients and found a sex-specific upregulation in male patients. Other genes within this locus were not dysregulated in RRMS patients. The findings suggest the existence of a common regulatory mechanism controlling miRNA expression in this region, regardless of the position of their genes. Further investigation is needed to determine whether the observed miRNA gene expression changes are involved in the development of RRMS or are a consequence of the disease progression.
Review
Biochemistry & Molecular Biology
Natalia Baulina, Ivan Kiselev, Olga Favorova
Summary: Multiple sclerosis (MS) is a chronic autoimmune neurodegenerative disease of the central nervous system that results from the interplay between genetic and non-genetic risk factors. Epigenetics serves as a crucial link between these factors, particularly in the manifestation of parent-of-origin effects. Imprinted genes may play a key role in the pathogenesis of MS, with disturbances in their expression potentially contributing to the development of the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Genetics & Heredity
Rujuan Dai, Zhuang Wang, S. Ansar Ahmed
Summary: Systemic lupus erythematosus (SLE) is a complex autoimmune disease affecting multiple organs, with DNA methylation and miRNAs playing key roles in its pathogenesis. The interaction between DNA methylation and miRNAs regulation impacts the expression of lupus-related miRNAs and DNA methylation status.
Article
Biochemistry & Molecular Biology
Mengying Yu, Yingxiang Liu, Zhuo Han, Wei Du, Bingxue Chen, Lei Zhang, Hongni Xue, Zihan Zhang, Zekun Guo
Summary: The gene dosage at the imprinted Dlk1-Dio3 locus is critical for cell growth and development. A high gene expression within the Dlk1-Dio3 region, especially the active expression of Gtl2, is a reliable marker for cell pluripotency. The DNA methylation state of the IG-DNA methylated regions (DMR) dominantly contributes to the control of gene expression in the Dlk1-Dio3 locus, but the precise mechanism is still unknown. In this study, the interaction of PGC7 with UHRF1 is found to be involved in maintaining DNA methylation and inducing DNA hypermethylation in the IG-DMR region.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2022)
Article
Genetics & Heredity
Heinrich Bente, Andrea M. Foerster, Nicole Lettner, Ortrun Mittelsten Scheidid
Summary: Paramutation is a form of non-Mendelian inheritance where gene expression changes when encountering specific genes, even after segregation. Initially discovered in plant pigmentation genes, it likely involves epigenetic mechanisms, resulting in stable intergenerational inheritance. This study in Arabidopsis thaliana provides insights into the complex process of paramutation, influenced by sRNAs, sequence of alleles, environmental conditions, and developmental stage, with unique features compared to other cases.
Article
Medicine, Research & Experimental
Yorihiro Iwasaki, Cagri Aksu, Monica Reyes, Birol Ay, Qing He, Murat Bastepe
Summary: Genetic defects of GNAS are responsible for multiple diseases, and abnormal imprinting at the GNAS A/B region causes pseudohypoparathyroidism type 1B. Utilizing a human embryonic stem cell model, we demonstrated the importance of the NESP-ICR in methylation and transcriptional silencing of the GNAS A/B region, and identified the STX16-ICR as a enhancer for NESP55 transcription. These findings advance our understanding of the pathogenesis of pseudohypoparathyroidism type 1B.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Plant Sciences
Yupeng Zhang, Tuomas Toivainen, Kathryn Mackenzie, Igor Yakovlev, Paal Krokene, Timo Hytonen, Paul E. Grini, Carl Gunnar Fossdal
Summary: Temperature conditions during embryogenesis and seed development can lead to epigenetic changes and phenotypic variation in plants. This study investigates the lasting effects of embryogenesis and seed development at two different temperatures (28 vs. 18°C) on woodland strawberry (Fragaria vesca). Significant differences were found in phenotypic features between plants from seeds produced at different temperatures, indicating a temperature-induced epigenetic memory-like response. DNA methylation marks and leaf transcriptomes were also affected by embryonic temperature in an ecotype-specific manner. However, there was variation in DNA methylation between individual plants within each temperature treatment, possibly due to allelic redistribution and epigenetic reprogramming.
PHYSIOLOGIA PLANTARUM
(2023)
Article
Oncology
Pingping Hou, Avnish Kapoor, Qiang Zhang, Jiexi Li, Chang-Jiun Wu, Jun Li, Zhengdao Lan, Ming Tang, Xingdi Ma, Jeffrey J. Ackroyd, Raghu Kalluri, Jianhua Zhang, Shan Jiang, Denise J. Spring, Y. Alan Wang, Ronald A. DePinho
Article
Oncology
Di Zhao, Li Cai, Xin Lu, Xin Liang, Jiexi Li, Peiwen Chen, Michael Ittmann, Xiaoying Shang, Shan Jiang, Haoyan Li, Chenling Meng, Ivonne Flores, Jian H. Song, James W. Horner, Zhengdao Lan, Chang-Jiun Wu, Jun Li, Qing Chang, Ko-Chien Chen, Guocan Wang, Pingna Deng, Denise J. Spring, Y. Alan Wang, Ronald A. DePinho
Article
Cell Biology
Emily Swanzey, Thomas F. McNamara, Effie Apostolou, Mamta Tahiliani, Matthias Stadtfeld
Article
Cell & Tissue Engineering
Simon E. Vidal, Alexander Polyzos, Kaushiki Chatterjee, Ly-sha Ee, Emily Swanzey, Jorge Morales-Valencia, Hongsu Wang, Chaitanya N. Parikh, Bhishma Amlani, Shengjiang Tu, Yixiao Gong, Valentina Snetkova, Jane A. Skok, Aristotelis Tsirigos, Sangyong Kim, Effie Apostolou, Matthias Stadtfeld
Article
Biochemistry & Molecular Biology
Bobbie Pelham-Webb, Alexander Polyzos, Luke Wojenski, Andreas Kloetgen, Jiexi Li, Dafne Campigli Di Giammartino, Theodore Sakellaropoulos, Aristotelis Tsirigos, Leighton Core, Effie Apostolou
Summary: This study elucidates the principles and mediators of molecular resetting in mouse pluripotent stem cells during self-renewal, including the asynchronous transcriptional and architectural resetting upon mitotic exit, and the potential bookmarking function of H3K27 acetylation.
Review
Cell Biology
Jiexi Li, Xingdi Ma, Deepavali Chakravarti, Shabnam Shalapour, Ronald A. DePinho
Summary: Colorectal cancer ranks as the third most common cancer in women, the fourth most common in men, and the fourth leading cause of cancer death globally. Incidence and mortality rates vary by race and ethnicity, with non-Hispanic blacks having the highest rates. In recent years, there has been a decline in the incidence of colorectal cancer in individuals over 50 years old.
GENES & DEVELOPMENT
(2021)
Article
Multidisciplinary Sciences
Yohei Yoshihama, Kyle A. LaBella, Eiru Kim, Lori Bertolet, Medina Colic, Jiexi Li, Xiaoying Shang, Chang-Jiun Wu, Denise J. Spring, Y. Alan Wang, Traver Hart, Ronald A. DePinho
Summary: Prostate cancer is a common cause of cancer deaths in men, especially when AR inhibitors are utilized. The study found that the histone demethylase JMJD1C plays a crucial role in AR-negative prostate cancer, with depletion inhibiting cell growth. Loss of AR or JMJD1C results in a modest TNF alpha signature, while combined loss leads to a significant up-regulation of TNF alpha, indicating TNF alpha signaling as a convergence point for AR and JMJD1C.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Chengmei Huang, Ruizhang Ou, Xiaoning Chen, Yaxin Zhang, Jiexi Li, Yihao Liang, Xiaohui Zhu, Lei Liu, Mingzhou Li, Dagui Lin, Junfeng Qiu, Guanglong Liu, Lingjie Zhang, Yuanyuan Wu, Huiyi Tang, Yanmin Liu, Li Liang, Yanqing Ding, Wenting Liao
Summary: SPON2 drives M2-TAM infiltration in the tumor microenvironment, playing an important role in colorectal cancer tumor growth and metastasis, suggesting its potential as a valuable biomarker guiding macrophage-targeting therapies.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Rumi Lee, Jiexi Li, Jun Li, Chang-Jiun Wu, Shan Jiang, Wen-Hao Hsu, Deepavali Chakravarti, Peiwen Chen, Kyle A. LaBella, Jing Li, Denise J. Spring, Di Zhao, Y. Alan Wang, Ronald A. DePinho
Summary: This study identifies critical effectors in the maintenance of APC-deficient colorectal cancer and demonstrates the relationship between APC/WNT pathway and kynurenine pathway signaling. It further determines the tumor-associated macrophage biology in APC-deficient colorectal cancer, informing genotype-specific therapeutic targets and the use of TDO2 inhibitors.
Article
Cell Biology
Gorkem Garipler, Congyi Lu, Alexis Morrissey, Lorena S. Lopez-Zepeda, Yingzhen Pei, Simon E. Vidal, Ana Paula Zen Petisco Fiore, Begum Aydin, Matthias Stadtfeld, Uwe Ohler, Shaun Mahony, Neville E. Sanjana, Esteban O. Mazzoni
Summary: The transcription factors ZBTB11 and ZFP131 are essential for maintaining pluripotency in embryonic stem cells. They repress the premature expression of pro-differentiation genes, preventing the loss of pluripotency.
Article
Multidisciplinary Sciences
Jiexi Li, Zhengdao Lan, Wenting Liao, James W. W. Horner, Xueping Xu, Jielin Liu, Yohei Yoshihama, Shan Jiang, Hong Seok Shim, Max Slotnik, Kyle A. A. LaBella, Chang-Jiun Wu, Kenneth Dunner Jr, Wen-Hao Hsu, Rumi Lee, Isha Khanduri, Christopher Terranova, Kadir Akdemir, Deepavali Chakravarti, Xiaoying Shang, Denise J. J. Spring, Y. Alan Wang, Ronald A. A. DePinho
Summary: Sex plays an important role in cancer incidence, spectrum, and outcomes, particularly in colorectal cancer (CRC) where men have higher metastases and mortality rates. A study using a murine CRC model revealed that oncogenic mutant KRAS (KRAS*) CRC in males showed higher metastases and worse outcomes. Further analysis found that the Y-chromosome gene histone demethylase KDM5D, driven by KRAS*-mediated activation of the STAT4 transcription factor, contributed to the sex differences in KRAS* CRC. Deletion of Kdm5d in cancer cells improved tight junction integrity, reduced invasiveness, and enhanced cancer cell killing by CD8(+) T cells. On the contrary, mice with a Kdm5d transgene had a higher propensity for invasive tumors. Therefore, the upregulation of Y chromosome KDM5D via KRAS*-STAT4 pathway disrupts cancer cell adhesion properties and tumor immunity, providing a potential therapeutic strategy for reducing metastasis risk in men with KRAS* CRC.
Meeting Abstract
Oncology
Jiexi Li, Zhengdao Lan, Wenting Liao, James W. Horner, Jielin Liu, Shan Jiang, Hong S. Shim, Max Slotnik, Kyle A. LaBella, Wen-Hao Hsu, Denise J. Spring, Y. Alan Wang, Ronald A. DePinho
Article
Cell Biology
Hong Seok Shim, James W. Horner, Chang-Jiun Wu, Jiexi Li, Zheng D. Lan, Shan Jiang, Xueping Xu, Wen-Hao Hsu, Tomasz Zal, Ivonne I. Flores, Pingna Deng, Yuan-Ta Lin, Li-Huei Tsai, Y. Alan Wang, Ronald A. DePinho
Summary: The research found that deficiency of telomerase reverse transcriptase (TERT) affects neuronal expression and accumulation of amyloid-beta in the brain, while maintaining normal levels of TERT helps reduce amyloid-beta accumulation and preserve cognitive function. Furthermore, the interaction between TERT, beta-catenin, and RNA polymerase II at gene promoters leads to the upregulation of gene networks governing synaptic signaling and learning processes.