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Transcription activator-like effectors

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https://www.readbyqxmd.com/read/29454785/lymphoid-tissue-inducer-a-divergent-member-of-the-ilc-family
#1
REVIEW
Chao Zhong, Mingzhu Zheng, Jinfang Zhu
Innate lymphoid cells (ILCs) that are capable of producing effector cytokines reminiscent of CD4+ T helper (Th) cells during infections and tissue inflammations have drawn much attention in the immunology field in recent years. Within the ILCs, the lymphoid tissue inducer (LTi) cells that play a critical role in lymphoid organogenesis were identified long before the establishment of the ILC concept. LTi cells, developed and functioning mainly at the fetal stage, and LTi-like cells, presumably generated during the adulthood, are regarded as a subset of type 3 ILCs (ILC3s) because they express the ILC3 lineage-defining transcription factor RORγt, and like other ILC3s, can produce an ILC3 signature cytokine IL-22 and initiate protective immune responses against extracellular bacteria...
February 13, 2018: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29453333/scleraxis-is-a-transcriptional-activator-that-regulates-the-expression-of-tenomodulin-a-marker-of-mature-tenocytes-and-ligamentocytes
#2
Chisa Shukunami, Aki Takimoto, Yuriko Nishizaki, Yuki Yoshimoto, Seima Tanaka, Shigenori Miura, Hitomi Watanabe, Tetsushi Sakuma, Takashi Yamamoto, Gen Kondoh, Yuji Hiraki
Tenomodulin (Tnmd) is a type II transmembrane glycoprotein predominantly expressed in tendons and ligaments. We found that scleraxis (Scx), a member of the Twist-family of basic helix-loop-helix transcription factors, is a transcriptional activator of Tnmd expression in tenocytes. During embryonic development, Scx expression preceded that of Tnmd. Tnmd expression was nearly absent in tendons and ligaments of Scx-deficient mice generated by transcription activator-like effector nucleases-mediated gene disruption...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29447390/pold3-is-required-for-genomic-stability-and-telomere-integrity-in-embryonic-stem-cells-and-meiosis
#3
Zhongcheng Zhou, Lingling Wang, Feixiang Ge, Peng Gong, Hua Wang, Feng Wang, Lingyi Chen, Lin Liu
Embryonic stem cells (ESCs) and meiosis are featured by relatively higher frequent homologous recombination associated with DNA double strand breaks (DSB) repair. Here, we show that Pold3 plays important roles in DSB repair, telomere maintenance and genomic stability of both ESCs and spermatocytes in mice. By attempting to generate Pold3 deficient mice using CRISPR/Cas9 or transcription activator-like effector nucleases, we show that complete loss of Pold3 (Pold3-/-) resulted in early embryonic lethality at E6...
February 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29440709/brca1-function-in-the-intra-s-checkpoint-is-activated-by-acetylation-via-a-pcaf-sirt1-axis
#4
Tyler J Lahusen, Seung-Jin Kim, Kai Miao, Zebin Huang, Xiaoling Xu, Chu-Xia Deng
Breast cancer associated gene 1 (BRCA1) function has been shown to be regulated by phosphorylation but the role of acetylation has not been determined. Therefore, we tested whether BRCA1 can be acetylated by the acetyltransferases P300/CBP-associated factor (pCAF), GCN5, and p300. p300 exhibited the highest level of BRCA1 acetylation; however, there was also a decrease in the total level of BRCA1. Therefore, we focused on pCAF and GCN5 because they both acetylated BRCA1 without affecting BRCA1 expression. Further analysis indicated that the acetylated form of BRCA1 is deacetylated by wild-type (WT) SIRT1, but not deacetylase mutant SIRT1, suggesting that SIRT1 is a specific deacetylase of BRCA1...
February 14, 2018: Oncogene
https://www.readbyqxmd.com/read/29438257/recent-insights-into-vascular-development-from-studies-in-zebrafish
#5
Ryota L Matsuoka, Didier Y R Stainier
PURPOSE OF REVIEW: Zebrafish has provided a powerful platform to study vascular biology over the past 25 years, owing to their distinct advantages for imaging and genetic manipulation. In this review, we summarize recent progress in vascular biology with particular emphasis on vascular development in zebrafish. RECENT FINDINGS: The advent of transcription activator-like effector nuclease and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 genome-editing technologies has dramatically facilitated reverse genetic approaches in zebrafish, as in other models...
February 12, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29435939/application-of-tale-based-approach-for-dissecting-functional-microrna-302-367-in-cellular-reprogramming
#6
Zhonghui Zhang, Wen-Shu Wu
MicroRNAs are small 18-24 nt single-stranded noncoding RNA molecules involved in many biological processes, including stemness maintenance and cellular reprogramming. Current methods used in loss-of-function studies of microRNAs have several limitations. Here, we describe a new approach for dissecting miR-302/367 functions by transcription activator-like effectors (TALEs), which are natural effector proteins secreted by Xanthomonas and Ralstonia bacteria. Knockdown of the miR-302/367 cluster uses the Kruppel-associated box repressor domain fused with specific TALEs designed to bind the miR-302/367 cluster promoter...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29434588/gata3-hdac6-and-bcl6-regulate-foxp3-treg-plasticity-and-determine-treg-conversion-into-either-novel-antigen-presenting-cell-like-treg-or-th1-treg
#7
Keman Xu, William Y Yang, Gayani Kanchana Nanayakkara, Ying Shao, Fan Yang, Wenhui Hu, Eric T Choi, Hong Wang, Xiaofeng Yang
We conducted an experimental database analysis to determine the expression of 61 CD4+ Th subset regulators in human and murine tissues, cells, and in T-regulatory cells (Treg) in physiological and pathological conditions. We made the following significant findings: (1) adipose tissues of diabetic patients with insulin resistance upregulated various Th effector subset regulators; (2) in skin biopsy from patients with psoriasis, and in blood cells from patients with lupus, effector Th subset regulators were more upregulated than downregulated; (3) in rosiglitazone induced failing hearts in ApoE-deficient (KO) mice, various Th subset regulators were upregulated rather than downregulated; (4) aortic endothelial cells activated by proatherogenic stimuli secrete several Th subset-promoting cytokines; (5) in Treg from follicular Th (Tfh)-transcription factor (TF) Bcl6 KO mice, various Th subset regulators were upregulated; whereas in Treg from Th2-TF GATA3 KO mice and HDAC6 KO mice, various Th subset regulators were downregulated, suggesting that Bcl6 inhibits, GATA3 and HDAC6 promote, Treg plasticity; and (6) GATA3 KO, and Bcl6 KO Treg upregulated MHC II molecules and T cell co-stimulation receptors, suggesting that GATA3 and BCL6 inhibit Treg from becoming novel APC-Treg...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29432786/oleic-acid-induces-the-novel-apolipoprotein-o-and-reduces-mitochondrial-membrane-potential-in-chicken-and-human-hepatoma-cells
#8
Anna M Weijler, Barbara Schmidinger, Stylianos Kapiotis, Hilde Laggner, Marcela Hermann
Non-alcoholic fatty liver disease (NAFLD) is marked by hepatic fat accumulation and reflects a spectrum of chronic liver diseases associated with obesity, impaired insulin sensitivity and dyslipidemia. Apolipoprotein O (ApoO) is a new member of the plasma apolipoprotein family that may play a role in lipid metabolism and electron transport activity of the mitochondrium. However, its physiological functions have not been elucidated yet. Based on our previous data in a non-mammalian experimental system [1], we hypothesized that hepatic expression of ApoO is tightly linked not only to diet-induced hepatosteatosis, but also to increased lipoprotein-production induced by, e...
February 9, 2018: Biochimie
https://www.readbyqxmd.com/read/29432547/fsh-pc-sce-complex-mediates-active-transcription-of-cubitus-interruptus-ci
#9
Xiangdong Lv, Hao Chen, Shuo Zhang, Zhao Zhang, Chenyu Pan, Yuanxin Xia, Jialin Fan, Wenqing Wu, Yi Lu, Lei Zhang, Hailong Wu, Yun Zhao
The Hedgehog (Hh) signaling pathway plays important roles in both embryonic development and adult tissue homeostasis. Such biological functions are mediated by the transcription factor Cubitus interruptus (Ci). Yet the transcriptional regulation of the effector Ci itself is poorly investigated. Through an RNAi-based genetic screen, we identified that female sterile (1) homeotic (Fsh), a transcription co-activator, directly activates Ci transcription. Biochemistry assays demonstrated physical interactions among Fsh,Sex combs extra (Sce) and Polycomb (Pc)...
February 8, 2018: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29423731/hiv-persistence-in-adipose-tissue-reservoirs
#10
REVIEW
Jacob Couturier, Dorothy E Lewis
PURPOSE OF REVIEW: The purpose of this review is to examine the evidence describing adipose tissue as a reservoir for HIV-1 and how this often expansive anatomic compartment contributes to HIV persistence. RECENT FINDINGS: Memory CD4 T cells and macrophages, the major host cells for HIV, accumulate in adipose tissue during HIV/SIV infection of humans and rhesus macaques. Whereas HIV and SIV proviral DNA is detectable in CD4 T cells of multiple fat depots in virtually all infected humans and monkeys examined, viral RNA is less frequently detected, and infected macrophages may be less prevalent in adipose tissue...
February 9, 2018: Current HIV/AIDS Reports
https://www.readbyqxmd.com/read/29423214/use-of-gene-editing-technology-to-introduce-targeted-modifications-in-pigs
#11
REVIEW
Junghyun Ryu, Randall S Prather, Kiho Lee
Pigs are an important resource in agriculture and serve as a model for human diseases. Due to their physiological and anatomical similarities with humans, pigs can recapitulate symptoms of human diseases, making them a useful model in biomedicine. However, in the past pig models have not been widely used partially because of the difficulty in genetic modification. The lack of true embryonic stem cells in pigs forced researchers to utilize genetic modification in somatic cells and somatic cell nuclear transfer (SCNT) to generate genetically engineered (GE) pigs carrying site-specific modifications...
2018: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/29393424/genetic-correction-of-adipose-tissue-derived-mesenchymal-stem-cells-mediated-by-talen-targeting-the-gdf5-gene
#12
Baofeng Li, Ying Zhang, Mei Li, Xiaoliang Zhao, Huibin Xie, Xiaoze Guo, Fei Wang, Hong Xia, Bei Chen
Stem cells and other associated cell types may be a potential alternative to treat various genetic disorders that currently do not benefit from traditional approaches. Functional recovery of cells could be induced via directional differentiation or genetic manipulation. In this study, mesenchymal stem cells (MSCs) were obtained from a patient with osteoarthritis (OA) carrying a functional single‑nucleotide polymorphism (SNP rs143383, C/T transition) within the 5'‑UTR of growth and differentiation factor 5 (GDF5) gene...
January 30, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29392354/advances-in-transcriptomics-of-plants
#13
Naghmeh Nejat, Abirami Ramalingam, Nitin Mantri
The current global population of 7.3 billion is estimated to reach 9.7 billion in the year 2050. Rapid population growth is driving up global food demand. Additionally, global climate change, environmental degradation, drought, emerging diseases, and salty soils are the current threats to global food security. In order to mitigate the adverse effects of these diverse agricultural productivity constraints and enhance crop yield and stress-tolerance in plants, we need to go beyond traditional and molecular plant breeding...
February 2, 2018: Advances in Biochemical Engineering/biotechnology
https://www.readbyqxmd.com/read/29390154/bacterial-gene-control-by-dna-looping-using-engineered-dimeric-transcription-activator-like-effector-tale-proteins
#14
Nicole A Becker, Tanya L Schwab, Karl J Clark, L James Maher
Genetic switches must alternate between states whose probabilities are dependent on regulatory signals. Classical examples of transcriptional control in bacteria depend on repressive DNA loops anchored by proteins whose structures are sensitive to small molecule inducers or co-repressors. We are interested in exploiting these natural principles to engineer artificial switches for transcriptional control of bacterial genes. Here, we implement designed homodimeric DNA looping proteins ('Transcription Activator-Like Effector Dimers'; TALEDs) for this purpose in living bacteria...
January 30, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29388081/loss-of-angelman-syndrome-protein-e6ap-disrupts-a-novel-antagonistic-estrogen-retinoic-acid-transcriptional-crosstalk-in-neurons
#15
Jimmy El Hokayem, Edwin Weeber, Zafar Nawaz
Angelman syndrome (AS) is a complex genetic disorder that affects the nervous system. AS affects an estimated 1 in 12,000 to 20,000 individuals. Characteristic features of AS includes developmental delay or intellectual disability, severe speech impairment, seizures, small head size (microcephaly), and problems with movement and balance (ataxia). AS individuals usually have microdeletion of the maternal copy of 15q11.2-15q13 region of chromosome 15. The E6-associated protein (E6AP, an E3 ubiquitin protein ligase enzyme) is encoded by the gene UBE3A, which is located in this region, and it has been shown that deregulation of E6AP gives rise to AS and neuropathology of autism spectrum disorders (ASDs) (e...
January 31, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29385539/foxg1-overexpression-in-neocortical-pyramids-stimulates-dendrite-elongation-via-hes1-and-pcreb1-upregulation
#16
Simone Chiola, Mihn Duc Do, Lucy Centrone, Antonello Mallamaci
The architecture of neocortical projection neurons is subject of a complex gene control. Here we demonstrated that Foxg1, a transcription factor gene which patterns the early rostral brain and sets the pace of telencephalic neuronogenesis, specifically stimulates dendrite elongation. This phenomenon occurs in vivo like in vitro, and it is detectable even upon moderate changes of Foxg1 expression levels. We found that Foxg1 acts by stimulating Hes1, which in turn upregulates pCreb1, a well-known pro-dendritogenic effector, and downregulates Syt and Ndr1, namely two established antagonizers of dendrite elongation...
January 28, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29383175/apancreatic-pigs-cloned-using-pdx1-disrupted-fibroblasts-created-via-talen-mediated-mutagenesis
#17
Jin-Dan Kang, Hyojin Kim, Long Jin, Qing Guo, Cheng-Du Cui, Wen-Xue Li, Seokjoong Kim, Jin-Soo Kim, Xi-Jun Yin
Pancreatic and duodenal homeobox 1 (PDX1) plays a crucial role in pancreas development, β-cell differentiation, and maintenance of mature β-cell function. In this study, we designed a strategy to produce PDX1-knockout (KO) pigs. A transcription activator-like effector nuclease (TALEN) pair targeting exon 1 of the swine PDX1 gene was constructed. Porcine fetal fibroblasts (PFFs) were transfected with the TALEN plasmids plus a surrogate reporter plasmid. PDX1-mutated PFFs were enriched by magnetic separation and used to produce homozygous PDX1-KO pigs via a two-step somatic cell nuclear transfer (SCNT) cloning process...
December 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29382771/defended-to-the-nines-25-years-of-resistance-gene-cloning-identifies-nine-mechanisms-for-r-protein-function
#18
Jiorgos Kourelis, Renier A L van der Hoorn
Plants display extensive genetic variation at resistance (R) gene loci for resistance to a variety of pathogens. The first R gene, Hm1, was cloned over 25 years ago, and many different R genes have since been identified and isolated. The encoded proteins have provided clues to diverse molecular mechanisms underlying immunity. The majority encode either cell-surface or intracellular receptors, and we present here a meta- analysis of 314 cloned R genes. We distinguish nine molecular mechanisms by which R proteins can elevate or trigger disease resistance...
January 30, 2018: Plant Cell
https://www.readbyqxmd.com/read/29363554/insight-into-the-molecular-mechanism-of-mir-192-regulating-escherichiacoli-resistance-in-piglets
#19
Li Sun, Sen Wu, Chao-Hui Dai, Shou-Yong Sun, Guo-Qiang Zhu, Sheng-Long Wu, Wen-Bin Bao
MicroRNAs (miRNAs) have important roles in many cellular processes, including cell proliferation, growth and development and disease control. Previous study demonstrated that the expression of two highly homologous miRNAs (miR-192 and 215) was upregulated in weaned piglets with Escherichia coli F18 infection. However, the potential molecular mechanism of miR-192 in regulating E. coli infection remains unclear in pigs. In this study, we analyzed the relationship between level of miR-192 and degree of E. coli resistance using transcription activator-like effector nuclease (TALEN), in vitro bacterial adhesion assays and target genes research...
January 23, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29361752/crispr-cas9-advancing-orthopoxvirus-genome-editing-for-vaccine-and-vector-development
#20
REVIEW
Arinze Okoli, Malachy I Okeke, Morten Tryland, Ugo Moens
The clustered regularly interspaced short palindromic repeat (CRISPR)/associated protein 9 (Cas9) technology is revolutionizing genome editing approaches. Its high efficiency, specificity, versatility, flexibility, simplicity and low cost have made the CRISPR/Cas9 system preferable to other guided site-specific nuclease-based systems such as TALENs (Transcription Activator-like Effector Nucleases) and ZFNs (Zinc Finger Nucleases) in genome editing of viruses. CRISPR/Cas9 is presently being applied in constructing viral mutants, preventing virus infections, eradicating proviral DNA, and inhibiting viral replication in infected cells...
January 22, 2018: Viruses
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