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Daniela A Grassi, Marie E Jönsson, Per Ludvik Brattås, Johan Jakobsson
TRIM28 is an epigenetic co-repressor protein that mediates transcriptional silencing. TRIM28 participates, together with the large family of Kruppel-associated box domain zinc finger proteins (KRAB-ZFP) transcription factors, in the repression of transposable elements (TE). Recent advances indicate that TRIM28-based repression of TEs occurs in the mammalian brain and may provide beneficial effects through the regulation of transcriptional networks. Here, we provide an overview of TRIM28-related functions, highlighting the role of controlling TEs in neural progenitor cells and discuss how this mechanism may have contributed to the evolution of the complex human brain...
March 6, 2018: Brain Research
Andreia Lee, Oya CingÖz, Yosef Sabo, Stephen P Goff
Moloney Murine Leukemia Virus (M-MLV) proviral DNA is transcriptionally silenced in embryonic cells by a large repressor complex tethered to the provirus by two sequence-specific DNA binding proteins, ZFP809 and YY1. A central component of the complex is Trim28, a scaffold protein that regulates many target genes involved in cell cycle progression, DNA damage responses, and viral gene expression. The silencing activity of Trim28, and its interactions with corepressors are often regulated by post-translational modifications such as sumoylation and phosphorylation...
January 26, 2018: Virology
Fan Li, Zhijie Wang, Gaochuan Lu
Aberrant expression of tripartite motif-containing protein 28 (TRIM28) has been demonstrated in several human cancers; however, its biological function and related mechanism in cervical cancer remain unclear. In this study, we compared TRIM28 expression between cervical cancer and adjacent normal tissues, and detected significant elevation in TRIM28 expression levels in the cervical cancer tissues. Moreover, TRIM28 overexpression promoted the proliferation, colony formation, and cell cycle progression of cervical cancer cell lines, as well as the growth of xenograft tumors in nude mice, whereas knockdown of TRIM28 had the opposite effects...
January 26, 2018: Oncology Reports
Jianshuang Li, Di Lu, Hong Dou, Huadie Liu, Kevin Weaver, Wenjun Wang, Jiada Li, Edward T H Yeh, Bart O Williams, Tao Yang, Ling Zheng
The development, growth, and renewal of skeletal tissues rely on the function of osteochondroprogenitors (OCPs). Protein sumoylation/desumoylation has emerged as a pivotal mechanism for stem cell/progenitor homeostasis, and excessive sumoylation has been associated with cell senescence and tissue aging, but its role in regulating OCP function is unclear. Here we show that postnatal loss of the desumoylase SUMO1/sentrin-specific peptidase 6 (SENP6) causes premature aging. OCP-specific SENP6 knockout mice exhibit smaller skeletons, with elevated apoptosis and cell senescence in OCPs and chondrocytes...
January 10, 2018: Nature Communications
Yu Tao, Ming-Ren Yen, Tsotne Chitiashvili, Haruko Nakano, Rachel Kim, Linzi Hosohama, Yao Chang Tan, Atsushi Nakano, Pao-Yang Chen, Amander T Clark
Transition from primed to naive pluripotency is associated with dynamic changes in transposable element (TE) expression and demethylation of imprinting control regions (ICRs). In mouse, ICR methylation and TE expression are each regulated by TRIM28; however, the role of TRIM28 in humans is less clear. Here, we show that a null mutation in TRIM28 causes significant alterations in TE expression in both the naive and primed states of human pluripotency, and phenotypically this has limited effects on self-renewal, instead causing a loss of germline competency...
December 26, 2017: Stem Cell Reports
Xiaofeng Bai, Hua Shi, Mingxi Yang, Yuanlin Wang, Zhaolin Sun, Shuxiong Xu
Human forkhead box P3 (FOXP3)+ cluster of differentiation (CD)25+CD4+ regulatory T cells (Tregs) are a type of T cell that express CD4, CD25 and FOXP3, which are critical for maintaining immune homeostasis. The present study aimed to determine the mechanisms underlying Treg function. The GSE11292 dataset was downloaded from the Gene Expression Omnibus, which included data from Treg cells at 19 time points (0‑360 min) with an equal interval of 20 min, and corresponding repeated samples. However, data for Treg cells at time point 120 min were missing...
December 29, 2017: Molecular Medicine Reports
Urszula Oleksiewicz, Marta Gładych, Ayush T Raman, Holger Heyn, Elisabetta Mereu, Paula Chlebanowska, Anastazja Andrzejewska, Barbara Sozańska, Neha Samant, Katarzyna Fąk, Paulina Auguścik, Marcin Kosiński, Joanna P Wróblewska, Katarzyna Tomczak, Katarzyna Kulcenty, Rafał Płoski, Przemysław Biecek, Manel Esteller, Parantu K Shah, Kunal Rai, Maciej Wiznerowicz
Reprogramming to induced pluripotent stem cells (iPSCs) and differentiation of pluripotent stem cells (PSCs) are regulated by epigenetic machinery. Tripartite motif protein 28 (TRIM28), a universal mediator of Krüppel-associated box domain zinc fingers (KRAB-ZNFs), is known to regulate both processes; however, the exact mechanism and identity of participating KRAB-ZNF genes remain unknown. Here, using a reporter system, we show that TRIM28/KRAB-ZNFs alter DNA methylation patterns in addition to H3K9me3 to cause stable gene repression during reprogramming...
December 12, 2017: Stem Cell Reports
Zhenzi Peng, Jun Wang, Bin Shan, Fulai Yuan, Bin Li, Yeping Dong, Wei Peng, Wenwen Shi, Yuanda Cheng, Yang Gao, Chunfang Zhang, Chaojun Duan
LncRNAs have emerged as a novel class of critical regulators of cancer. We aimed to construct a landscape of lncRNAs and their potential target genes in lung adenocarcinoma. Genome-wide expression of lncRNAs and mRNAs was determined using microarray. qRT-PCR was performed to validate the expression of the selected lncRNAs in a cohort of 42 tumor tissues and adjacent normal tissues. R and Bioconductor were used for data analysis. A total of 3045 lncRNAs were differentially expressed between the paired tumor and normal tissues (1048 up and 1997 down)...
November 10, 2017: Scientific Reports
Lei Liu, Lei Zhang, Jianping Wang, Xuerong Zhao, Qian Xu, Yanjie Lu, Yanzhen Zuo, Long Chen, Jia Du, Yali Lian, Qin Zhang
TRIM28 is a well‑known transcriptional co‑repressor of Kruppel‑associated box zinc finger proteins. The authors previously demonstrated that TRIM28 small interfering (si)RNA decreases cell proliferation and inhibits cell cycle progression in non‑small cell lung cancer (NSCLC) cell lines. The present study further demonstrated that the stable silencing of TRIM28 expression by a specific siRNA lentivirus vector significantly inhibited the growth and exerted obvious anti‑tumor effects in nude mice. The results of the terminal deoxynucleotidyl transferase‑mediated deoxyuridine triphosphate nick‑end labeling assay indicated that TRIM28 knockdown increased apoptosis...
January 2018: Molecular Medicine Reports
Nicolas Altemose, Nudrat Noor, Emmanuelle Bitoun, Afidalina Tumian, Michael Imbeault, J Ross Chapman, A Radu Aricescu, Simon R Myers
PRDM9 binding localizes almost all meiotic recombination sites in humans and mice. However, most PRDM9-bound loci do not become recombination hotspots. To explore factors that affect binding and subsequent recombination outcomes, we mapped human PRDM9 binding sites in a transfected human cell line and measured PRDM9-induced histone modifications. These data reveal varied DNA-binding modalities of PRDM9. We also find that human PRDM9 frequently binds promoters, despite their low recombination rates, and it can activate expression of a small number of genes including CTCFL and VCX ...
October 26, 2017: ELife
Si-Jian Pan, Jie Ren, Hong Jiang, Wei Liu, Liang-Yun Hu, Yi-Xin Pan, Bomin Sun, Qing-Fang Sun, Liu-Guan Bian
Melanoma antigen A6 (MAGEA6)/TRIM28 complex is a cancer-specific ubiquitin ligase, which degradates tumor suppressor protein AMP-activated protein kinase (AMPK). We show that MAGEA6 is uniquely expressed in human glioma tissues and cells, which is correlated with AMPKα1 downregulation. It is yet absent in normal brain tissues and human astrocytes/neuronal cells. MAGEA6 knockdown by targeted-shRNA in glioma cells restored AMPKα1 expression, causing mTORC1 in-activation and cell death/apoptosis. Reversely, AMPKα1 knockdown or mutation ameliorated glioma cell death by MAGEA6 shRNA...
January 1, 2018: Cancer Letters
Alex J Gooding, Bing Zhang, Fereshteh Kenari Jahanbani, Hannah L Gilmore, Jenny C Chang, Saba Valadkhan, William P Schiemann
Long noncoding RNAs (lncRNAs) have emerged as potent regulators of breast cancer development and progression, including the metastatic spread of disease. Through in silico and biological analyses, we identified a novel lncRNA, BMP/OP-Responsive Gene (BORG), whose expression directly correlates with aggressive breast cancer phenotypes, as well as with metastatic competence and disease recurrence in multiple clinical cohorts. Mechanistically, BORG elicits the metastatic outgrowth of latent breast cancer cells by promoting the localization and transcriptional repressive activity of TRIM28, which binds BORG and induces substantial alterations in carcinoma proliferation and survival...
October 5, 2017: Scientific Reports
Jian Luo, Yiyuan Zhang, Yanhua Guo, Hong Tang, Haixia Wei, Shouren Liu, Xinhua Wang, Limin Wang, Ping Zhou
DNA methylation is an essential epigenetic modification involved in regulating gene expression and maintaining epigenetic information across generations. However, how these marks are recognized and interpreted to activate or repress imprinted genes is not fully understood. Preliminary evidence describes the transcriptional repressor TRIM28 as a key regulator of imprinted gene expression during and after early genome-wide reprogramming. Aberrant expression of imprinted genes maybe one possible cause of incomplete epigenetic reprogramming and low efficiency in somatic cell nuclear transfer...
December 30, 2017: Gene
B Deng, S Zhang, Y Zhang, Y Miao, X Meng, K Guo
Tripartite motif containing 28 (TRIM28) is a transcriptional corepressor of Kruppel-associated box zinc finger protein, which has been reported to participate in carcinogenesis. Nonetheless, whether TRIM28 plays a role in the metastasis of ovarian carcinoma (OC) is unclear and requires further investigation. In this study, two OC cell lines (A2780 and OVCAR-3) with stable low expression of TRIM28 were established via RNA interference. We found that the migratory and invasive ability of TRIM28-silenced OC cells significantly decreased...
September 12, 2017: Neoplasma
Hongliang Liu, Qing Wei, Chenyang Huang, Yong Zhang, Zekun Guo
DNA methylation is an important epigenetic modification that needs to be carefully controlled as a prerequisite for normal early embryogenesis. Compelling evidence now suggests that four maternal-effect proteins, primordial germ cell 7 (PGC7), zinc finger protein 57 (ZFP57), tripartite motif-containing 28 (TRIM28) and DNA methyltransferase (cytosine-5) 1 (DNMT1) are involved in the maintenance of DNA methylation. However, it is still not fully understood how these maternal-effect proteins maintain the DNA methylation imprint...
September 4, 2017: International Journal of Molecular Sciences
Patrycja Czerwińska, Sylwia Mazurek, Maciej Wiznerowicz
Since the first discovery in 1996, the engagement of TRIM28 in distinct aspects of cellular biology has been extensively studied resulting in identification of a complex nature of TRIM28 protein. In this review, we summarize core biological functions of TRIM28 that emerge from TRIM28 multi-domain structure and possessed enzymatic activities. Moreover, we will discuss whether the complexity of TRIM28 engagement in cancer biology makes TRIM28 a possible candidate for targeted anti-cancer therapy. Briefly, we will demonstrate the role of TRIM28 in regulation of target gene transcription, response to DNA damage, downregulation of p53 activity, stimulation of epithelial-to-mesenchymal transition, stemness sustainability, induction of autophagy and regulation of retrotransposition, to provide the answer whether TRIM28 functions as a stimulator or inhibitor of tumorigenesis...
August 29, 2017: Journal of Biomedical Science
Gabriela Ecco, Michael Imbeault, Didier Trono
Krüppel-associated box domain zinc finger proteins (KRAB-ZFPs) are the largest family of transcriptional regulators in higher vertebrates. Characterized by an N-terminal KRAB domain and a C-terminal array of DNA-binding zinc fingers, they participate, together with their co-factor KAP1 (also known as TRIM28), in repression of sequences derived from transposable elements (TEs). Until recently, KRAB-ZFP/KAP1-mediated repression of TEs was thought to lead to irreversible silencing, and the evolutionary selection of KRAB-ZFPs was considered to be just the host component of an arms race against TEs...
August 1, 2017: Development
Marta Klimczak, Patrycja Czerwińska, Sylwia Mazurek, Barbara Sozańska, Przemysław Biecek, Andrzej Mackiewicz, Maciej Wiznerowicz
Cellular reprogramming proceeds in a stepwise pathway initiated by binding and transcription of pluripotency factors followed by genome-wide epigenetic changes. Priming events, such as erasure of DNA methylation and chromatin remodeling determines the success of pluripotency acquisition later. Therefore, growing efforts are made to understand epigenetic regulatory network that makes reprogramming possible and efficient. Here, we analyze the role of transcriptional corepressor TRIM28, involved in heterochromatin formation, during the process of reprogramming of mouse somatic cells into induced pluripotent stem cells (iPS cells)...
August 2017: Stem Cell Research
Poppy Simmonds, Erick Loomis, Edward Curry
BACKGROUND: Profiles of DNA methylation of many tissues relevant in human disease have been obtained from microarrays and are publicly available. These can be used to generate maps of chromatin compartmentalization, demarcating open and closed chromatin across the genome. Additionally, large sets of genome-wide transcription factor binding profiles have been made available thanks to ChIP-seq technology. METHODS: We have identified genomic regions with altered chromatin compartmentalization in prostate adenocarcinoma tissue relative to normal prostate tissue, using DNA methylation microarray data from The Cancer Genome Atlas...
June 7, 2017: Genome Medicine
Salem A El-Aarag, Amal Mahmoud, Medhat H Hashem, Hatem Abd Elkader, Alaa E Hemeida, Mahmoud ElHefnawi
BACKGROUND: Lung cancer is a leading cause of cancer-related death worldwide and is the most commonly diagnosed cancer. Like other cancers, it is a complex and highly heterogeneous disease involving multiple signaling pathways. Identifying potential therapeutic targets is critical for the development of effective treatment strategies. METHODS: We used a systems biology approach to identify potential key regulatory factors in smoking-induced lung cancer. We first identified genes that were differentially expressed between smokers with normal lungs and those with cancerous lungs, then integrated these differentially expressed genes (DEGs) with data from a protein-protein interaction database to build a network model with functional modules for pathway analysis...
June 7, 2017: BMC Medical Genomics
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