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https://www.readbyqxmd.com/read/29728366/the-hush-complex-cooperates-with-trim28-to-repress-young-retrotransposons-and-new-genes
#1
Luisa Robbez-Masson, Christopher H C Tie, Lucia Conde, Hale Tunbak, Connor Husovsky, Iva A Tchasovnikarova, Richard T Timms, Javier Herrero, Paul J Lehner, Helen M Rowe
Retrotransposons encompass half of the human genome and contribute to the formation of heterochromatin, which provides nuclear structure and regulates gene expression. Here, we asked if the human silencing hub (HUSH) complex is necessary to silence retrotransposons and whether it collaborates with TRIM28 and the chromatin remodeler ATRX at specific genomic loci. We show that the HUSH complex contributes to de novo repression and DNA methylation of a SVA retrotransposon reporter. By using naïve vs. primed mouse pluripotent stem cells, we reveal a critical role for the HUSH complex in naïve cells, implicating it in programming epigenetic marks in development...
May 4, 2018: Genome Research
https://www.readbyqxmd.com/read/29656892/cancer-germline-antigen-expression-discriminates-clinical-outcome-to-ctla-4-blockade
#2
Sachet A Shukla, Pavan Bachireddy, Bastian Schilling, Christina Galonska, Qian Zhan, Clyde Bango, Rupert Langer, Patrick C Lee, Daniel Gusenleitner, Derin B Keskin, Mehrtash Babadi, Arman Mohammad, Andreas Gnirke, Kendell Clement, Zachary J Cartun, Eliezer M Van Allen, Diana Miao, Ying Huang, Alexandra Snyder, Taha Merghoub, Jedd D Wolchok, Levi A Garraway, Alexander Meissner, Jeffrey S Weber, Nir Hacohen, Donna Neuberg, Patrick R Potts, George F Murphy, Christine G Lian, Dirk Schadendorf, F Stephen Hodi, Catherine J Wu
CTLA-4 immune checkpoint blockade is clinically effective in a subset of patients with metastatic melanoma. We identify a subcluster of MAGE-A cancer-germline antigens, located within a narrow 75 kb region of chromosome Xq28, that predicts resistance uniquely to blockade of CTLA-4, but not PD-1. We validate this gene expression signature in an independent anti-CTLA-4-treated cohort and show its specificity to the CTLA-4 pathway with two independent anti-PD-1-treated cohorts. Autophagy, a process critical for optimal anti-cancer immunity, has previously been shown to be suppressed by the MAGE-TRIM28 ubiquitin ligase in vitro...
April 6, 2018: Cell
https://www.readbyqxmd.com/read/29651155/epigenetic-activation-during-t-helper-17-cell-differentiation-is-mediated-by-tripartite-motif-containing-28
#3
Yu Jiang, Ying Liu, Huiping Lu, Shao-Cong Sun, Wei Jin, Xiaohu Wang, Chen Dong
Epigenetic regulation is important for T-cell fate decision. Although STAT3 is known to initiate Th17 differentiation program, the downstream mechanism is unclear. Here we show that Tripartite motif containing 28 (Trim28) expression in Th17 cells is required for Th17-mediated cytokine production and experimental autoimmune diseases. Genome-wide occupancy analysis reveals that TRIM28-bound regions overlap with almost all Th17-specific super-enhancers (SE), and that those SEs are impaired by the deficiency of STAT3 or TRIM28, but not of RORγt...
April 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29581850/interactome-analysis-of-transforming-growth-factor-%C3%AE-activated-kinase-1-in-helicobacter-pylori-infected-cells-revealed-novel-regulators-tripartite-motif-28-and-cdc37
#4
Olga Sokolova, Thilo Kähne, Kenneth Bryan, Michael Naumann
Transforming growth factor-β (TGFβ)-activated kinase 1 (TAK1) plays a central role in controlling the cellular pro-inflammatory response via the activation of the nuclear factor κB (NF-κB)- and mitogen-activated protein (MAP) kinases-dependent transcriptional programs. Here, we show that depletion of TAK1 and the TAK1-binding proteins TAB1 and TAB2 affects NF-κB, JNK and p38 phosphorylation and suppresses NF-κB activity in AGS cells infected with Helicobacter pylori or stimulated with the cytokines TNF and IL-1β...
March 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29569972/expression-of-trim28-correlates-with-proliferation-and-bortezomib-induced-apoptosis-in-b-cell-non-hodgkin-lymphoma
#5
Pei-Pei Zhang, Da-Zhi Ding, Bing Shi, Shu-Qing Zhang, Ling-Li Gu, Yu-Chan Wang, Chun Cheng
Tripartite motif containing 28 (TRIM28) as a transcriptional co-repressor has been reported playing a role in regulating DNA damage response (DDR), cell differentiation, immune response, and tumorigenesis. The present study was performed to explore the biological function and clinical significance of TRIM28 in B-cell non-Hodgkin lymphoma (B-NHL). Results of the study displayed that high expression of TRIM28 was positively associated with the poorer survival of B-NHL patients as an independent prognostic factor...
March 23, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29522722/trim28-and-the-control-of-transposable-elements-in-the-brain
#6
REVIEW
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
https://www.readbyqxmd.com/read/29407374/characterization-of-interaction-between-trim28-and-yy1-in-silencing-proviral-dna-of-moloney-murine-leukemia-virus
#7
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...
March 2018: Virology
https://www.readbyqxmd.com/read/29393469/trim28-promotes-cervical-cancer-growth-through-the-mtor-signaling-pathway
#8
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...
April 2018: Oncology Reports
https://www.readbyqxmd.com/read/29321472/desumoylase-senp6-maintains-osteochondroprogenitor-homeostasis-by-suppressing-the-p53-pathway
#9
Jianshuang Li, Di Lu, Hong Dou, Huadie Liu, Kevin Weaver, Wenjun Wang, Jiada Li, Edward T H Yeh, Bart O Williams, Ling Zheng, Tao Yang
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
https://www.readbyqxmd.com/read/29290627/trim28-regulated-transposon-repression-is-required-for-human-germline-competency-and-not-primed-or-naive-human-pluripotency
#10
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...
January 9, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29286140/identification-of-key-genes-implicated-in-the-suppressive-function-of-human-foxp3-cd25-cd4-regulatory-t-cells-through-the-analysis-of-time%C3%A2-series-data
#11
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...
March 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29198826/trim28-and-interacting-krab-znfs-control-self-renewal-of-human-pluripotent-stem-cells-through-epigenetic-repression-of-pro-differentiation-genes
#12
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
https://www.readbyqxmd.com/read/29127420/genome-wide-analyses-of-long-noncoding-rna-expression-profiles-in-lung-adenocarcinoma
#13
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
https://www.readbyqxmd.com/read/29115614/downregulation-of-trim28-inhibits-growth-and-increases-apoptosis-of-nude-mice-with-non%C3%A2-small-cell-lung-cancer-xenografts
#14
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
https://www.readbyqxmd.com/read/29072575/a-map-of-human-prdm9-binding-provides-evidence-for-novel-behaviors-of-prdm9-and-other-zinc-finger-proteins-in-meiosis
#15
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
https://www.readbyqxmd.com/read/29024810/magea6-promotes-human-glioma-cell-survival-via-targeting-ampk%C3%AE-1
#16
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
https://www.readbyqxmd.com/read/28983112/the-lncrna-borg-drives-breast-cancer-metastasis-and-disease-recurrence
#17
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
https://www.readbyqxmd.com/read/28947302/trim28-regulates-igf2-h19-and-dlk1-gtl2-imprinting-by-distinct-mechanisms-during-sheep-fibroblast-proliferation
#18
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
https://www.readbyqxmd.com/read/28895414/knockdown-of-tripartite-motif-containing-28-suppresses-the-migration-invasion-and-epithelial-mesenchymal-transition-in-ovarian-carcinoma-cells-through-down-regulation-of-wnt-%C3%AE-catenin-signaling-pathway
#19
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
https://www.readbyqxmd.com/read/28869544/potential-roles-of-intrinsic-disorder-in-maternal-effect-proteins-involved-in-the-maintenance-of-dna-methylation
#20
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
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