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Véronique Hugouvieux, Catarina S Silva, Agnès Jourdain, Arnaud Stigliani, Quentin Charras, Vanessa Conn, Simon J Conn, Cristel C Carles, François Parcy, Chloe Zubieta
The MADS transcription factors (TF) constitute an ancient family of TF found in all eukaryotes that bind DNA as obligate dimers. Plants have dramatically expanded the functional diversity of the MADS family during evolution by adding protein-protein interaction domains to the core DNA-binding domain, allowing the formation of heterotetrameric complexes. Tetramerization of plant MADS TFs is believed to play a central role in the evolution of higher plants by acting as one of the main determinants of flower formation and floral organ specification...
March 19, 2018: Nucleic Acids Research
Emily G Kaye, Matthew Booker, Jesse V Kurland, Alexander E Conicella, Nicolas L Fawzi, Martha L Bulyk, Michael Y Tolstorukov, Erica Larschan
Little is known about how variation in sequence composition alters transcription factor occupancy to precisely recruit large transcription complexes. A key model for understanding how transcription complexes are targeted is the Drosophila dosage compensation system in which the male-specific lethal (MSL) transcription complex specifically identifies and regulates the male X chromosome. The chromatin-linked adaptor for MSL proteins (CLAMP) zinc-finger protein targets MSL to the X chromosome but also binds to GA-rich sequence elements throughout the genome...
March 20, 2018: Cell Reports
Noel Lianga, Carole Doré, Erin K Kennedy, Elaine Yeh, Elizabeth C Williams, Camille Marie Fortinez, Alick Wang, Kerry S Bloom, Adam D Rudner
Anaphase onset is an irreversible cell cycle transition that is triggered by the activation of the protease Separase. Separase cleaves the Mcd1 (also known as Scc1) subunit of Cohesin, a complex of proteins that physically links sister chromatids, triggering sister chromatid separation. Separase is regulated by the degradation of the anaphase inhibitor Securin which liberates Separase from inhibitory Securin/Separase complexes. In many organisms, Securin is not essential suggesting that Separase is regulated by additional mechanisms...
March 21, 2018: PLoS Genetics
Xiao-Ming Wang, Yang Liu, Yu-Xia Fan, Zheng Liu, Qing-Ling Yuan, Meng Jia, Geng Zu-Shi, Ling Gu, Xiu-Bo Lu
Background LncRNA PTCSC3 is a tumor suppressor in thyroid cancer, and its role in drug resistance of anaplastic thyroid cancer (ATC) to chemotherapy drug doxorubicin was investigated in this study. Methods Expression of RNA and protein was analyzed by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze the expression rate of CD133+ cells. The endogenous expression of related genes was modulated by recombinant plasmids and cell transfection. Combination condition and interaction between PTCSC3 and STAT3 were determined by RIP and RNA pull-down assay, respectively...
March 21, 2018: Cancer Biology & Therapy
Andrew VonHandorf, Francisco Javier Sánchez-Martín, Jacek Biesiada, Hongxia Zhang, Xiang Zhang, Mario Medvedovic, Alvaro Puga
Hexavalent chromium compounds are well-established respiratory carcinogens used in industrial processes. While inhalation exposure constitutes an occupational risk affecting mostly chromium workers, environmental exposure from drinking water is a widespread gastrointestinal cancer risk, affecting millions of people throughout the world. Cr(VI) is genotoxic, forming protein-Cr-DNA adducts and silencing tumor suppressor genes, but its mechanism of action at the molecular level is poorly understood. Our prior work using FAIRE showed that Cr(VI) disrupted the binding of transcription factors CTCF and AP-1 to their cognate chromatin sites...
March 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Nicolette Kapp, Xiao X Stander, Barend A Stander
This project investigated the in-vitro effects of a glycolytic inhibitor, 3-bromopyruvate (3-BrP), in combination with and a new in silico-designed inhibitor of the bromodomain-4 (BRD-4) protein, ITH-47, on the U937 acute myeloid leukemia cell line. 3-BrP is an agent that targets the altered metabolism of cancer cells by interfering with glucose metabolism in the glycolytic pathway. ITH-47 is an acetyl-lysine inhibitor that displaces bromdomain 4 proteins from chromatin by competitively binding to the acetyl-lysine recognition pocket of this bromodomain and extraterminal (BET) BRD protein, thereby preventing transcription of cancer-associated genes and further cell growth...
March 20, 2018: Anti-cancer Drugs
Joana Torres, Remo Monti, Ariane L Moore, Makiko Seimiya, Yanrui Jiang, Niko Beerenwinkel, Christian Beisel, Jorge V Beira, Renato Paro
Tumor initiation is often linked to a loss of cellular identity. Transcriptional programs determining cellular identity are preserved by epigenetically-acting chromatin factors. Although such regulators are among the most frequently mutated genes in cancer, it is not well understood how an abnormal epigenetic condition contributes to tumor onset. In this work, we investigated the gene signature of tumors caused by disruption of the Drosophila epigenetic regulator, polyhomeotic (ph). In larval tissue ph mutant cells show a shift towards an embryonic-like signature...
March 21, 2018: ELife
Anjan Debnath, Andrew T Nelson, Angélica Silva-Olivares, Mineko Shibayama, Dionicio Siegel, James H McKerrow
Primary amebic meningoencephalitis (PAM) is a fatal infection caused by the free-living ameba Naegleria fowleri , popularly known as the "brain-eating ameba." The drugs of choice in treating PAM are the antifungal amphotericin B and an antileishmanial miltefosine, but these are not FDA-approved for this indication and use of amphotericin B is associated with severe adverse effects. Moreover, very few patients treated with the combination therapy have survived PAM. Therefore, development of efficient drugs is a critical unmet need to avert future deaths of children...
2018: Frontiers in Microbiology
Elizabeth S Silagi, Philip Batista, Irving M Shapiro, Makarand V Risbud
The integrity of the avascular nucleus pulposus (NP) phenotype plays a crucial role in the maintenance of intervertebral disc health. While advances have been made to define the molecular phenotype of healthy NP cells, the functional relevance of several of these markers remains unknown. In this study, we test the hypothesis that expression of Carbonic Anhydrase III (CAIII), a marker of the notochordal NP, is hypoxia-responsive and functions as a potent antioxidant without a significant contribution to pH homeostasis...
March 20, 2018: Scientific Reports
Ruifang Li, Ruiling Zhang, Yanhui Yang, Xueqin Wang, Yanjie Yi, Pei Fan, Zhengwei Liu, Chen Chen, Junpeng Chang
CGA-N12 is an antifungal peptide derived from human chromogranin A. In our previous investigation, CGA-N12 was found to have specific anti-candidal activity, though the mechanism of action remained unclear. Herein, we investigated the effects of CGA-N12 on mitochondria. We found that CGA-N12 induced an over-generation of intracellular reactive oxygen species and dissipation in mitochondrial membrane potential, in which the former plays key roles in the initiation of apoptosis and the latter is a sign of the cell apoptosis...
March 20, 2018: Biochemical Journal
Xin-Xin Yu, Wei-Lin Qiu, Liu Yang, Lin-Chen Li, Yu-Wei Zhang, Cheng-Ran Xu
Pancreatic endocrine lineages are derived from pancreatic progenitors that undergo a cell fate transition requiring a switch from low to high Ngn3 expression. However, the underlying chromatin regulatory mechanisms are unclear. Here, we performed epigenomic analysis of gene regulatory loci featuring histone marks in cells with low or high level of Ngn3 expression. In combination with transcriptomic analysis, we discovered that in Ngn3-high cells, the removal of H3K27me3 was associated with the activation of key transcription factors and the establishment of primed and active enhancers...
March 20, 2018: Development
Tanvi Shashikant, Jian Ming Khor, Charles A Ettensohn
BACKGROUND: The developmental gene regulatory network (GRN) that underlies skeletogenesis in sea urchins and other echinoderms is a paradigm of GRN structure, function, and evolution. This transcriptional network is deployed selectively in skeleton-forming primary mesenchyme cells (PMCs) of the early embryo. To advance our understanding of this model developmental GRN, we used genome-wide chromatin accessibility profiling to identify and characterize PMC cis-regulatory modules (CRMs)...
March 20, 2018: BMC Genomics
Kasturi Chatterjee, Sayantan Jana, Pramathes DasMahapatra, Snehasikta Swarnakar
Endometriosis, characterized by extrauterine development of endometrial glands and stroma, is associated with increased risk of ovarian cancer development. In the present study, we investigated the role of matrix metalloproteinase-7 (MMP-7) on epithelial-mesenchymal transition (EMT) during ovarian endometriosis ( N = 40) progression. We found that the expressions of EMT markers such as vimentin, slug, and N-cadherin were significantly elevated in late stages of ovarian endometriosis compared with those found in early stages...
March 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Jebi Sudan, Meenakshi Raina, Ravinder Singh
Plants have evolved various defense mechanisms including morphological adaptations, cellular pathways, specific signalling molecules and inherent immunity to endure various abiotic stresses during different growth stages. Most of the defense mechanisms are controlled by stress-responsive genes by transcribing and translating specific genes. However, certain modifications of DNA and chromatin along with small RNA-based mechanisms have also been reported to regulate the expression of stress-responsive genes and constitute another line of defense for plants in their struggle against stresses...
March 2018: 3 Biotech
Jingjiang Pi, Jie Liu, Tao Zhuang, Lin Zhang, Huimin Sun, Xiaoli Chen, Qian Zhao, Yashu Kuang, Sheng Peng, Xiaohui Zhou, Zuoren Yu, Ting Tao, Brian Tomlinson, Paul Chan, Ying Tian, Huimin Fan, Zhongmin Liu, Xiangjian Zheng, Edward Morrisey, Yuzhen Zhang
Rationale: Angiogenesis is critical for embryonic development and microRNAs fine-tune this process, but the underlying mechanisms remain incompletely understood. Methods: Endothelial cell (EC) specific miR302-367 line was used as gain-of-function and anti-miRs as loss-of-function models to investigate the effects of miR302-367 on developmental angiogenesis with embryonic hindbrain vasculature as an in vivo model and fibrin gel beads and tube formation assay as in vitro models. Cell migration was evaluated by Boyden chamber and scratch wound healing assay and cell proliferation by cell count, MTT assay, Ki67 immunostaining and PI cell cycle analysis...
2018: Theranostics
Duanyang Zhai, Chunhui Cui, Lang Xie, Lianxu Cai, Jinlong Yu
Metastasis is the primary cause of mortality in colorectal cancer (CRC), the mechanism of which remains unclear. In the present study, by detecting mRNA expression using a reverse transcription-quantitative polymerase chain reaction (qPCR), it was revealed that sterol regulatory element-binding protein 1 (SREBP1) is highly expressed in CRC. Using a cell wound healing assay and a cell invasion assay, a novel metastasis-promoting role for SREBP1 in CRC was identified. Furthermore, snail family transcriptional repressor 1 (SNAIL) was identified as a key downstream effector of SREBP1 in CRC by the use of small interfering RNA against SNAIL...
April 2018: Oncology Letters
Anniina Vihervaara, Fabiana M Duarte, John T Lis
Proteotoxic stress, that is, stress caused by protein misfolding and aggregation, triggers the rapid and global reprogramming of transcription at genes and enhancers. Genome-wide assays that track transcriptionally engaged RNA polymerase II (Pol II) at nucleotide resolution have provided key insights into the underlying molecular mechanisms that regulate transcriptional responses to stress. In addition, recent kinetic analyses of transcriptional control under heat stress have shown how cells 'prewire' and rapidly execute genome-wide changes in transcription while concurrently becoming poised for recovery...
March 19, 2018: Nature Reviews. Genetics
Dai Hatakeyama, Masaki Shoji, Seiya Yamayoshi, Rina Yoh, Naho Ohmi, Shiori Takenaka, Ayaka Saitoh, Yumie Arakaki, Aki Masuda, Tsugunori Komatsu, Rina Nagano, Masahiro Nakano, Takeshi Noda, Yoshihiro Kawaoka, Takashi Kuzuhara
Histone acetylation plays crucial roles in transcriptional regulation and chromatin organization. Viral RNA of the influenza virus interacts with its nucleoprotein (NP), whose function corresponds to that of eukaryotic histones. NP regulates viral replication and has been shown to undergo acetylation by the CREB-binding protein (CBP) from the host. However, whether NP is the target of other host acetyltransferases is unknown. Here, we show that influenza virus NP undergoes acetylation by the two host acetyltransferases GCN5 and P300/CBP-associated factor (PCAF) and that this modification affects viral polymerase activities...
March 19, 2018: Journal of Biological Chemistry
Christina M Ferrer, Marielle Alders, Alex V Postma, Seonmi Park, Mark A Klein, Murat Cetinbas, Eva Pajkrt, Astrid Glas, Silvana van Koningsbruggen, Vincent M Christoffels, Marcel M A M Mannens, Lia Knegt, Jean-Pierre Etchegaray, Ruslan I Sadreyev, John M Denu, Gustavo Mostoslavsky, Merel C van Maarle, Raul Mostoslavsky
It has been well established that histone and DNA modifications are critical to maintaining the equilibrium between pluripotency and differentiation during early embryogenesis. Mutations in key regulators of DNA methylation have shown that the balance between gene regulation and function is critical during neural development in early years of life. However, there have been no identified cases linking epigenetic regulators to aberrant human development and fetal demise. Here, we demonstrate that a homozygous inactivating mutation in the histone deacetylase SIRT6 results in severe congenital anomalies and perinatal lethality in four affected fetuses...
March 19, 2018: Genes & Development
Alice Pasini, Oliver J Brand, Gisli Jenkins, Alan J Knox, Linhua Pang
Cyclooxygenase-2 (COX-2), with its main antifibrotic metabolite PGE2 , is regarded as an antifibrotic gene. Repressed COX-2 expression and deficient PGE2 have been shown to contribute to the activation of lung fibroblasts and excessive deposition of collagen in pulmonary fibrosis. We have previously demonstrated that COX-2 expression in lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) is epigenetically silenced and can be restored by epigenetic inhibitors. This study aimed to investigate whether COX-2 downregulation induced by the profibrotic cytokine transforming growth factor-β1 (TGF-β1) in normal lung fibroblasts could be prevented by epigenetic inhibitors...
March 16, 2018: Biochimica et Biophysica Acta
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