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Georges Abboud, Jessica Stanfield, Vikas Tahiliani, Pritesh Desai, Tarun E Hutchinson, Kyle J Lorentsen, Jonathan J Cho, Dorina Avram, Shahram Salek-Ardakani
CD8(+) T cells play an important role in host resistance to many viral infections, but the underlying transcriptional mechanisms governing their differentiation and functionality remain poorly defined. By using a highly virulent systemic and respiratory poxvirus infection in mice, we show that the transcription factor Bcl11b provides a dual trigger that sustains the clonal expansion of virus-specific effector CD8(+) T cells, while simultaneously suppressing the expression of surface markers associated with short-lived effector cell (SLEC) differentiation...
2016: Frontiers in Immunology
Laura Whitton, Donna Cosgrove, Christopher Clarkson, Denise Harold, Kimberley Kendall, Alex Richards, Kiran Mantripragada, Michael J Owen, Michael C O'Donovan, James Walters, Annette Hartmann, Betina Konte, Dan Rujescu, Michael Gill, Aiden Corvin, Stephen Rea, Gary Donohoe, Derek W Morris
Epigenetic mechanisms are an important heritable and dynamic means of regulating various genomic functions, including gene expression, to orchestrate brain development, adult neurogenesis, and synaptic plasticity. These processes when perturbed are thought to contribute to schizophrenia pathophysiology. A core feature of schizophrenia is cognitive dysfunction. For genetic disorders where cognitive impairment is more severe such as intellectual disability, there are a disproportionally high number of genes involved in the epigenetic regulation of gene transcription...
December 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Yong Yu, Jason C H Tsang, Cui Wang, Simon Clare, Juexuan Wang, Xi Chen, Cordelia Brandt, Leanne Kane, Lia S Campos, Liming Lu, Gabrielle T Belz, Andrew N J McKenzie, Sarah A Teichmann, Gordon Dougan, Pentao Liu
Innate lymphoid cells (ILCs) functionally resemble T lymphocytes in cytotoxicity and cytokine production but lack antigen-specific receptors, and they are important regulators of immune responses and tissue homeostasis. ILCs are generated from common lymphoid progenitors, which are subsequently committed to innate lymphoid lineages in the α-lymphoid progenitor, early innate lymphoid progenitor, common helper innate lymphoid progenitor and innate lymphoid cell progenitor compartments. ILCs consist of conventional natural killer cells and helper-like cells (ILC1, ILC2 and ILC3)...
September 29, 2016: Nature
Valentin Le Douce, Faezeh Forouzanfar, Sebastian Eilebrecht, Benoit Van Driessche, Amina Ait-Ammar, Roxane Verdikt, Yoshihito Kurashige, Céline Marban, Virginie Gautier, Ermanno Candolfi, Arndt G Benecke, Carine Van Lint, Olivier Rohr, Christian Schwartz
Among many cellular transcriptional regulators, Bcl11b/CTIP2 and HGMA1 have been described to control the establishment and the persistence of HIV-1 latency in microglial cells, the main viral reservoir in the brain. In this present work, we identify and characterize a transcription factor i.e. HIC1, which physically interacts with both Bcl11b/CTIP2 and HMGA1 to co-regulate specific subsets of cellular genes and the viral HIV-1 gene. Our results suggest that HIC1 represses Tat dependent HIV-1 transcription...
October 11, 2016: Scientific Reports
Jun Inoue, Yusuke Ihara, Daisuke Tsukamoto, Keisuke Yasumoto, Tsutomu Hashidume, Kenya Kamimura, Yuji Nakai, Shigeki Hirano, Makoto Shimizu, Ryo Kominami, Ryuichiro Sato
The differentiation of preadipocytes into adipocytes is controlled by several transcription factors, including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), which are known as master regulators of adipogenesis. BCL11B is a zinc finger-type transcription factor that regulates the development of the skin and central nervous and immune systems. Here, we found that BCL11B was expressed in the white adipose tissue (WAT), particularly the subcutaneous WAT and that BCL11B(-/-) mice had a reduced amount of subcutaneous WAT...
2016: Scientific Reports
Erica Manesso, Hao Yuan Kueh, George Freedman, Ellen V Rothenberg, Carsten Peterson
BACKGROUND/OBJECTIVES: A cascade of gene activations under the control of Notch signalling is required during T-cell specification, when T-cell precursors gradually lose the potential to undertake other fates and become fully committed to the T-cell lineage. We elucidate how the gene/protein dynamics for a core transcriptional module governs this important process by computational means. METHODS: We first assembled existing knowledge about transcription factors known to be important for T-cell specification to form a minimal core module consisting of TCF-1, GATA-3, BCL11B, and PU...
2016: PloS One
Deniz Cizmeci, Emma L Dempster, Olivia L Champion, Sariqa Wagley, Ozgur E Akman, Joann L Prior, Orkun S Soyer, Jonathan Mill, Richard W Titball
The potential for epigenetic changes in host cells following microbial infection has been widely suggested, but few examples have been reported. We assessed genome-wide patterns of DNA methylation in human macrophage-like U937 cells following infection with Burkholderia pseudomallei, an intracellular bacterial pathogen and the causative agent of human melioidosis. Our analyses revealed significant changes in host cell DNA methylation, at multiple CpG sites in the host cell genome, following infection. Infection induced differentially methylated probes (iDMPs) showing the greatest changes in DNA methylation were found to be in the vicinity of genes involved in inflammatory responses, intracellular signalling, apoptosis and pathogen-induced signalling...
2016: Scientific Reports
Katia Georgopoulos
No abstract text is available yet for this article.
July 19, 2016: Nature Immunology
Hao Yuan Kueh, Mary A Yui, Kenneth K H Ng, Shirley S Pease, Jingli A Zhang, Sagar S Damle, George Freedman, Sharmayne Siu, Irwin D Bernstein, Michael B Elowitz, Ellen V Rothenberg
During T cell development, multipotent progenitors relinquish competence for other fates and commit to the T cell lineage by turning on Bcl11b, which encodes a transcription factor. To clarify lineage commitment mechanisms, we followed developing T cells at the single-cell level using Bcl11b knock-in fluorescent reporter mice. Notch signaling and Notch-activated transcription factors collaborate to activate Bcl11b expression irrespectively of Notch-dependent proliferation. These inputs work via three distinct, asynchronous mechanisms: an early locus 'poising' function dependent on TCF-1 and GATA-3, a stochastic-permissivity function dependent on Notch signaling, and a separate amplitude-control function dependent on Runx1, a factor already present in multipotent progenitors...
August 2016: Nature Immunology
Jiangquan Liao, Benjun Wei, Hengwen Chen, Yongmei Liu, Jie Wang
BACKGROUND: Xuesaitong soft capsule (XST) which consists of panax notoginseng saponin (PNS) has been used to treat ischemic cerebrovascular diseases in China. The therapeutic mechanism of XST has not been elucidated yet from prospective of genomics and bioinformatics. METHODS: A transcriptome analysis was performed to review series concerning middle cerebral artery occlusion (MCAO) rat model and XST intervention after MCAO from Gene Expression Omnibus (GEO) database...
2016: American Journal of Translational Research
Mohammad Nizam Uddin, Dil Afroz Sultana, Kyle J Lorentsen, Jonathan J Cho, Mariana E Kirst, Mark L Brantly, Danielle Califano, Derek B Sant'Angelo, Dorina Avram
Invariant natural killer T (iNKT) cells are innate-like T cells that recognize glycolipid antigens and play critical roles in regulation of immune responses. Based on expression of the transcription factors (TFs) Tbet, Plzf, and Rorγt, iNKT cells have been classified in effector subsets that emerge in the thymus, namely, iNKT1, iNKT2, and iNKT17. Deficiency in the TF Bcl11b in double-positive (DP) thymocytes has been shown to cause absence of iNKT cells in the thymus and periphery due to defective self glycolipid processing and presentation by DP thymocytes and undefined intrinsic alterations in iNKT precursors...
July 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
Hirofumi Rokutan, Fumie Hosoda, Natsuko Hama, Hiromi Nakamura, Yasushi Totoki, Eisaku Furukawa, Erika Arakawa, Shoko Ohashi, Tomoko Urushidate, Hironori Satoh, Hiroko Shimizu, Keiko Igarashi, Shinichi Yachida, Hitoshi Katai, Hirokazu Taniguchi, Masashi Fukayama, Tatsuhiro Shibata
Mucinous gastric carcinoma (MGC) is a unique subtype of gastric cancer with a poor survival outcome. Comprehensive molecular profiles and putative therapeutic targets of MGC remain undetermined. We subjected 16 tumour-normal tissue pairs to whole-exome sequencing (WES) and an expanded set of 52 tumour-normal tissue pairs to subsequent targeted sequencing. The latter focused on 114 genes identified by WES. Twenty-two histologically differentiated MGCs (D-MGCs) and 46 undifferentiated MGCs (U-MGCs) were analysed...
October 2016: Journal of Pathology
Marion Dubuissez, Ingrid Loison, Sonia Paget, Han Vorng, Saliha Ait-Yahia, Olivier Rohr, Anne Tsicopoulos, Dominique Leprince
The transcription factor BCL11B/CTIP2 is a major regulatory protein implicated in various aspects of development, function and survival of T cells. Mitogen-activated protein kinase (MAPK)-mediated phosphorylation and SUMOylation modulate BCL11B transcriptional activity, switching it from a repressor in naive murine thymocytes to a transcriptional activator in activated thymocytes. Here, we show that BCL11B interacts via its conserved N-terminal MSRRKQ motif with endogenous MTA1 and MTA3 proteins to recruit various NuRD complexes...
July 1, 2016: Molecular and Cellular Biology
R Simon, L Baumann, J Fischer, F A Seigfried, E De Bruyckere, P Liu, N A Jenkins, N G Copeland, H Schwegler, S Britsch
The dentate gyrus is one of the only two brain regions where adult neurogenesis occurs. Throughout life, cells of the neuronal stem cell niche undergo proliferation, differentiation and integration into the hippocampal neural circuitry. Ongoing adult neurogenesis is a prerequisite for the maintenance of adult hippocampal functionality. Bcl11b, a zinc finger transcription factor, is expressed by postmitotic granule cells in the developing as well as adult dentate gyrus. We previously showed a critical role of Bcl11b for hippocampal development...
April 2016: Genes, Brain, and Behavior
Sajjad Karim, Zeenat Mirza, Adeel G Chaudhary, Adel M Abuzenadah, Mamdooh Gari, Mohammed H Al-Qahtani
Toxicity induced by radiation therapy is a curse for cancer patients undergoing treatment. It is imperative to understand and define an ideal condition where the positive effects notably outweigh the negative. We used a microarray meta-analysis approach to measure global gene-expression before and after radiation exposure. Bioinformatic tools were used for pathways, network, gene ontology and toxicity related studies. We found 429 differentially expressed genes at fold change >2 and p-value <0.05. The most significantly upregulated genes were synuclein alpha (SNCA), carbonic anhydrase I (CA1), X-linked Kx blood group (XK), glycophorin A and B (GYPA and GYPB), and hemogen (HEMGN), while downregulated ones were membrane-spanning 4-domains, subfamily A member 1 (MS4A1), immunoglobulin heavy constant mu (IGHM), chemokine (C-C motif) receptor 7 (CCR7), BTB and CNC homology 1 transcription factor 2 (BACH2), and B-cell CLL/lymphoma 11B (BCL11B)...
2016: International Journal of Molecular Sciences
Ellen V Rothenberg, Jonas Ungerbäck, Ameya Champhekar
T-lymphocyte development branches off from other lymphoid developmental programs through its requirement for sustained environmental signals through the Notch pathway. In the thymus, Notch signaling induces a succession of T-lineage regulatory factors that collectively create the T-cell identity through distinct steps. This process involves both the staged activation of T-cell identity genes and the staged repression of progenitor-cell-inherited regulatory genes once their roles in self-renewal and population expansion are no longer needed...
2016: Advances in Immunology
Kasra Nikouei, Ana B Muñoz-Manchado, Jens Hjerling-Leffler
In the nervous system, BCL11B is crucial for the development of deep layer corticospinal projection neurons and striatal medium spiny neurons and is often used as a marker for the aforementioned cell types. However, the expression of BCL11B in subtypes of non-excitatory neurons in the primary somatosensory cortex (S1) has not been reported in the mouse. In this study we show that BCL11B is extensively expressed in S1 GABAergic interneurons, throughout the three main subgroups (somatostatin-, parvalbumin- and 5HT3a-expresssing)...
January 2016: Journal of Chemical Neuroanatomy
Kateryna Kyrylkova, Urszula T Iwaniec, Kenneth A Philbrick, Mark Leid
The transcription factor BCL11B plays essential roles during development of the immune, nervous, and cutaneous systems. Here we show that BCL11B is expressed in both osteogenic and sutural mesenchyme of the developing craniofacial complex. Bcl11b(-/-) mice exhibit increased proliferation of osteoprogenitors, premature osteoblast differentiation, and enhanced skull mineralization leading to synostoses of facial and calvarial sutures. Ectopic expression of Fgfr2c, a gene implicated in craniosynostosis in mice and humans, and that of Runx2 was detected within the affected sutures of Bcl11b(-/-) mice...
July 15, 2016: Developmental Biology
Xin Huang, Suxia Geng, Jianyu Weng, Zesheng Lu, Lingji Zeng, Minming Li, Chengxin Deng, Xiuli Wu, Yangqiu Li, Xin Du
BACKGROUND: Previous study showed that downregulated BCL11B expression in T cell acute lymphoblastic leukemia (T-ALL) cell line Molt-4 inhibited cell proliferation and induce apoptosis, which may be related to PHTF1 gene overexpression. The objective of this study was to investigate the expression of PHTF1 and related genes in ALL and further explore its function in T-ALL cell lines. METHODS: Real-time PCR was used to determine the gene expression level of PHTF1 in hematologic malignancies...
2015: Cancer Cell International
Brian W Kunkle, James Jaworski, Sandra Barral, Badri Vardarajan, Gary W Beecham, Eden R Martin, Laura S Cantwell, Amanda Partch, Thomas D Bird, Wendy H Raskind, Anita L DeStefano, Regina M Carney, Michael Cuccaro, Jeffrey M Vance, Lindsay A Farrer, Alison M Goate, Tatiana Foroud, Richard P Mayeux, Gerard D Schellenberg, Jonathan L Haines, Margaret A Pericak-Vance
INTRODUCTION: Few high penetrance variants that explain risk in late-onset Alzheimer's disease (LOAD) families have been found. METHODS: We performed genome-wide linkage and identity-by-descent (IBD) analyses on 41 non-Hispanic white families exhibiting likely dominant inheritance of LOAD, and having no mutations at known familial Alzheimer's disease (AD) loci, and a low burden of APOE ε4 alleles. RESULTS: Two-point parametric linkage analysis identified 14 significantly linked regions, including three novel linkage regions for LOAD (5q32, 11q12...
January 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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