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Chromatin modulation

Bernardo Pérez-Zamorano, Sandra Rosas-Madrigal, Oscar Arturo Migueles Lozano, Manuel Castillo Méndez, Verónica Valverde-Garduño
The innate immune response of Anopheles gambiae involves the transcriptional upregulation of effector genes. Therefore, the cis-regulatory sequences and their cognate binding factors play essential roles in the mosquito's immune response. However, the genetic control of the mosquito's innate immune response is not yet fully understood. To gain further insight on the elements, the factors and the potential mechanisms involved, an open chromatin profiling was carried out on A. gambiae-derived immune-responsive cells...
2017: PloS One
Xiucai Pan, Yuan Fang, Xueming Yang, Dongyang Zheng, Lifen Chen, Lei Wang, Jin Xiao, Xiu-E Wang, Kai Wang, Zhukuan Cheng, Hengxiu Yu, Wenli Zhang
BACKGROUND: The role of histone modifications in the DNA damage response has been extensively studied in non-plant systems, including mammals and yeast. However, there is a lack of detailed evidence showing how chromatin dynamics, either an individual mark or combined chromatin states, participate in regulating differentially expressed genes in the plant DNA damage response. RESULTS: In this study, we used RNA-seq and ChIP-seq to show that differentially expressed genes (DEGs), in response to ionizing radiation (IR), might be involved in different pathways responsible for the DNA damage response...
October 12, 2017: BMC Genomics
Yetao Xu, Zhiping Ge, Erbao Zhang, Qing Zuo, Shiyun Huang, Nana Yang, Dan Wu, Yuanyuan Zhang, Yanzi Chen, Haoqin Xu, Huan Huang, Zhiyan Jiang, Lizhou Sun
Due to limited treatment options, pre-eclampsia (PE) is associated with fetal perinatal and maternal morbidity and mortality. During the causes of PE, failure of uterine spiral artery remodeling which might be related to functioning abnormally of trophoblast cells, result in the occurrence and progression of PE. Recently, abnormal expression of long non-coding RNAs (lncRNAs), as imperative regulators involved in human diseases progression (included PE), which has been indicated by increasing evidence. In this research, we found that TUG1, a lncRNA, was markedly reduced in placental samples from patients with PE...
October 12, 2017: Cell Death & Disease
Mariano Oppikofer, Meredith Sagolla, Benjamin Haley, Hui-Min Zhang, Sarah K Kummerfeld, Jawahar Sudhamsu, E Megan Flynn, Tianyi Bai, Jennifer Zhang, Claudio Ciferri, Andrea G Cochran
Members of the ISWI family of chromatin remodelers mobilize nucleosomes to control DNA accessibility and, in some cases, are required for recovery from DNA damage. However, it remains poorly understood how the non-catalytic ISWI subunits BAZ1A and BAZ1B might contact chromatin to direct the ATPase SMARCA5. Here, we find that the plant homeodomain of BAZ1A, but not that of BAZ1B, has the unusual function of binding DNA. Furthermore, the BAZ1A bromodomain has a non-canonical gatekeeper residue and binds relatively weakly to acetylated histone peptides...
October 11, 2017: Nature Communications
Roberta Tarallo, Giorgio Giurato, Giuseppina Bruno, Maria Ravo, Francesca Rizzo, Annamaria Salvati, Luca Ricciardi, Giovanna Marchese, Angela Cordella, Teresa Rocco, Valerio Gigantino, Biancamaria Pierri, Giovanni Cimmino, Luciano Milanesi, Concetta Ambrosino, Tuula A Nyman, Giovanni Nassa, Alessandro Weisz
BACKGROUND: The RNA-binding protein Argonaute 2 (AGO2) is a key effector of RNA-silencing pathways It exerts a pivotal role in microRNA maturation and activity and can modulate chromatin remodeling, transcriptional gene regulation and RNA splicing. Estrogen receptor beta (ERβ) is endowed with oncosuppressive activities, antagonizing hormone-induced carcinogenesis and inhibiting growth and oncogenic functions in luminal-like breast cancers (BCs), where its expression correlates with a better prognosis of the disease...
October 6, 2017: Genome Biology
Dongbo Liu, Hongping Miao, Yuanyin Zhao, Xia Kang, Shenglan Shang, Wei Xiang, Rongchen Shi, Along Hou, Rui Wang, Kun Zhao, Yingzhe Liu, Yue Ma, Huan Luo, Hongming Miao, Fengtian He
BACKGROUND: Chronic inflammation is causally linked to the carcinogenesis and progression of most solid tumors. LPTS is a well-identified tumor suppressor by inhibiting telomerase activity and cancer cell growth. However, whether and how LPTS is regulated by inflammation signaling is still incompletely elucidated. METHODS: Real-time PCR and western blotting were used to determine the expression of p65 and LPTS. Reporter gene assay, electrophoretic mobility shift assay and chromatin immunoprecipitation were performed to decipher the regulatory mechanism between p65 and LPTS...
October 10, 2017: Cell Communication and Signaling: CCS
Yunxie Wei, Guoyin Liu, Yujing Bai, Feiyu Xia, Chaozu He, Haitao Shi
Similar to the situation in animals, melatonin biosynthesis is regulated by four sequential enzymatic steps in plants. Although the melatonin synthesis genes have been identified in various plants, the upstream transcription factors of them remain unknown. In this study on cassava (Manihot esculenta), we found that MeWRKY79 and heat-shock transcription factor 20 (MeHsf20) targeted the W-box and the heat-stress elements (HSEs) in the promoter of N-acetylserotonin O-methyltransferase 2 (MeASMT2), respectively...
August 26, 2017: Journal of Experimental Botany
Min Hee Choi, Monica Palanichamy Kala, Jin Rong Ow, Vinay Kumar Rao, Sudha Suriyamurthy, Reshma Taneja
Myogenic differentiation is accompanied by alterations in the chromatin states, which permit or restrict the transcriptional machinery and thus impact distinctive gene expression profiles. The mechanisms by which higher-order chromatin remodeling is associated with gene activation and silencing during differentiation is not fully understood. In this study, we provide evidence that the euchromatic lysine methyltransferase GLP regulates heterochromatin organization and myogenic differentiation. Interestingly, GLP represses expression of the methyl-binding protein MeCP2 that induces heterochromatin clustering during differentiation...
August 23, 2017: Journal of Molecular Cell Biology
Venizelos Papayannopoulos
Neutrophils are innate immune phagocytes that have a central role in immune defence. Our understanding of the role of neutrophils in pathogen clearance, immune regulation and disease pathology has advanced dramatically in recent years. Web-like chromatin structures known as neutrophil extracellular traps (NETs) have been at the forefront of this renewed interest in neutrophil biology. The identification of molecules that modulate the release of NETs has helped to refine our view of the role of NETs in immune protection, inflammatory and autoimmune diseases and cancer...
October 9, 2017: Nature Reviews. Immunology
Allison J Richard, Hardy Hang, Jacqueline M Stephens
STAT5 proteins play a role in adipocyte development and function, but their specific functions are largely unknown. To this end, we used an unbiased MS-based approach to identify novel STAT5-interacting proteins. We observed that STAT5A bound the E1β and E2 subunits of the pyruvate dehydrogenase complex (PDC). Whereas STAT5A typically localizes to the cytosol or nucleus, PDC normally resides within the mitochondrial matrix where it converts pyruvate to acetyl-CoA. We employed affinity purification and immunoblotting to validate the interaction between STAT5A and PDC subunits in murine and human cultured adipocytes, as well as in adipose tissue...
October 5, 2017: Journal of Biological Chemistry
Monica Soldi, Tommaso Mari, Luciano Nicosia, Daniele Musiani, Gianluca Sigismondo, Alessandro Cuomo, Giulio Pavesi, Tiziana Bonaldi
The integrated activity of cis-regulatory elements fine-tunes transcriptional programs of mammalian cells by recruiting cell type-specific as well as ubiquitous transcription factors (TFs). Despite their key role in modulating transcription, enhancers are still poorly characterized at the molecular level, and their limited DNA sequence conservation in evolution and variable distance from target genes make their unbiased identification challenging. The coexistence of high mono-methylation and low tri-methylation levels of lysine 4 of histone H3 is considered a signature of enhancers, but a comprehensive view of histone modifications associated to enhancers is still lacking...
September 13, 2017: Nucleic Acids Research
Hai-Jian Sun, Xing-Sheng Ren, Xiao-Qing Xiong, Yun-Zhi Chen, Ming-Xia Zhao, Jue-Jin Wang, Ye-Bo Zhou, Ying Han, Qi Chen, Yue-Hua Li, Yu-Ming Kang, Guo-Qing Zhu
Inflammation is involved in pathogenesis of hypertension. NLRP3 inflammasome activation is a powerful mediator of inflammatory response via caspase-1 activation. The present study was designed to determine the roles and mechanisms of NLRP3 inflammasome in phenotypic modulation and proliferation of vascular smooth muscle cells (VSMCs) in hypertension. Experiments were conducted in spontaneously hypertensive rats (SHR) and primary aortic VSMCs. NLRP3 inflammasome activation was observed in the media of aorta in SHR and in the VSMCs from SHR...
October 5, 2017: Cell Death & Disease
Stefan Nagel, Claudia Pommerenke, Corinna Meyer, Maren Kaufmann, Roderick A F MacLeod, Hans G Drexler
NKL homeobox gene MSX1 is physiologically expressed in lymphoid progenitors and subsequently downregulated in developing T- and B-cells. In contrast, elevated expression levels of MSX1 persist in mature natural killer (NK)-cells, indicating a functional role in this compartment. While T-cell acute lymphoblastic leukemia (T-ALL) subsets exhibit aberrant overexpression of MSX1, we show here that in malignant NK-cells the level of MSX1 transcripts is aberrantly downregulated. Chromosomal deletions at 4p16 hosting the MSX1 locus have been described in NK-cell leukemia patients...
September 15, 2017: Oncotarget
Ravi Jahagirdar, Sarah Attwell, Suzana Marusic, Alison Bendele, Narmada Shenoy, Kevin G McLure, Dean Gilham, Karen Norek, Henrik C Hansen, Raymond Yu, Jennifer Tobin, Gregory S Wagner, Peter R Young, Norman Cw Wong, Ewelina Kulikowski
Bromodomain and extra-terminal (BET) domain proteins are chromatin adapters that bind acetylated histone marks via two tandem bromodomains (BD1 and BD2) to regulate gene transcription. BET proteins are involved in transcriptional reprogramming in response to inflammatory stimuli. BET bromodomain inhibitors (BETi) that are non-selective for BD1 or BD2 have recognized anti-inflammatory properties in vitro and counter pathology in models of inflammation or autoimmune disease. While both BD1 and BD2 bind acetylated histone residues, they may independently regulate expression of BET sensitive genes...
September 29, 2017: Molecular Pharmacology
Catherine Rhee, Bum-Kyu Lee, Samuel Beck, Lucy LeBlanc, Haley O Tucker, Jonghwan Kim
Direct reprogramming can be achieved by forced expression of master transcription factors. Yet how such factors mediate repression of initial cell-type-specific genes while activating target cell-type-specific genes is unclear. Through embryonic stem (ES) to trophoblast stem (TS)-like cell reprogramming by introducing individual TS cell-specific 'CAG' factors (Cdx2, Arid3a and Gata3), we interrogate their chromosomal target occupancies, modulation of global transcription and chromatin accessibility at the initial stage of reprogramming...
September 29, 2017: Nucleic Acids Research
Scott T Younger, John L Rinn
The tumor suppressor p53 is a well-characterized transcription factor that can bind gene promoters and regulate target gene transcription in response to DNA damage. Recent studies, however, have revealed that p53 binding events occur predominantly within regulatory enhancer elements. The effect of p53 binding on enhancer function has not been systematically evaluated. Here, we perform a genome-scale analysis of enhancer activity from p53-bound sequences using a series of massively parallel reporter assays (MPRAs) coupled with the assay for transposase-accessible chromatin (ATAC-Seq)...
September 29, 2017: Nucleic Acids Research
Tonghai Huang, Guangsuo Wang, Lin Yang, Bin Peng, Yuxin Wen, Guanggui Ding, Zheng Wang
Lung cancer is the leading cause of cancer-related death worldwide. Despite the advancement in surgery and chemotherapy, the prognosis of patients with advanced lung cancer is still poor. Yin Yang-1 (YY1) is a multifunctional transcription factor that exhibits positive and negative control on a large number of cellular and viral genes. In this study, we showed that the expression of YY1 is upregulated in lung cancer tissues as compared to adjacent normal tissues. Patients with higher expression of YY1 had larger tumor size, poor differentiation, higher TNM stage, and lymph node metastasis...
October 3, 2017: DNA and Cell Biology
Zeng Fang, Yunfeng Yi, Ganggang Shi, Songqi Li, Songlin Chen, Ying Lin, Zhi Li, Zhimin He, Wen Li, Shuping Zhong
Brf1 (TFIIB-related factor 1) modulates the transcription of RNA Pol III genes (polymerase-dependent genes). Upregulation of Pol III genes enhances tRNA and 5S RNA production, and increases the translational capacity of cells to promote cell transformation and tumor development. However, the significance of Brf1 overexpression in human breast cancer (HBC) remains to be investigated. Here, we investigate whether Brf1 expression is increased in the samples of HBC, and we explore its molecular mechanism and the significance of Brf1 expression in HBC...
October 3, 2017: Molecular Oncology
Nicola Cornella, Toma Tebaldi, Lisa Gasperini, Jarnail Singh, Richard A Padgett, Annalisa Rossi, Paolo Macchi
The heterogeneous nuclear ribonucleoproteins (hnRNPs) form a large family of RNA-binding proteins that exert numerous functions in RNA metabolism. RALY is a member of the hnRNP family that binds poly-U rich elements within several RNAs and regulates the expression of specific transcripts. RALY is upregulated in different types of cancer, and its downregulation impairs cell cycle progression. However, RALY's role in regulating RNA levels remains elusive. Here, we show that numerous genes coding for factors involved in transcription and cell cycle regulation exhibit an altered expression in RALY-downregulated HeLa cells, consequently causing impairments in transcription, cell proliferation and cell cycle progression...
September 27, 2017: Journal of Biological Chemistry
Hongchao Cao, Shengjie Zhang, Shifang Shan, Chao Sun, Yan Li, Hui Wang, Shuxian Yu, Yi Liu, Feifan Guo, Qiwei Zhai, Yu-Cheng Wang, Jingjing Jiang, Hui Wang, Jun Yan, Wei Liu, Hao Ying
Nuclear receptors (NRs) regulate gene transcription by recruiting coregulators, involved in chromatin remodeling and assembly of the basal transcription machinery. The NR-associated protein ligand-dependent corepressor (LCoR) has previously been shown to suppress hepatic lipogenesis by decreasing the binding of steroid receptor coactivators to thyroid hormone receptor. However, the role of LCoR in adipogenesis has not been established. Here, we show that LCoR expression is reduced in the early stage of adipogenesis in vitro...
September 26, 2017: Journal of Biological Chemistry
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