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https://www.readbyqxmd.com/read/27807919/extended-exome-sequencing-identifies-bach2-as-a-novel-major-risk-locus-for-addison-s-disease
#1
D Eriksson, M Bianchi, N Landegren, J Nordin, F Dalin, A Mathioudaki, G N Eriksson, L Hultin-Rosenberg, J Dahlqvist, H Zetterqvist, Å Karlsson, Å Hallgren, F H G Farias, E Murén, K M Ahlgren, A Lobell, G Andersson, K Tandre, S R Dahlqvist, P Söderkvist, L Rönnblom, A-L Hulting, J Wahlberg, O Ekwall, P Dahlqvist, J R S Meadows, S Bensing, K Lindblad-Toh, O Kämpe, G R Pielberg
BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology. METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls...
November 2, 2016: Journal of Internal Medicine
https://www.readbyqxmd.com/read/27777084/crosstalk-between-the-gut-and-the-liver-via-susceptibility-loci-novel-advances-in-inflammatory-bowel-disease-and-autoimmune-liver-disease
#2
Xinyang Li, Jun Shen, Zhihua Ran
Inflammatory bowel disease (IBD) is an autoimmune disorder characterized by chronic, relapsing intestinal inflammation. Autoimmune liver disease (AILD) may be involved in IBD as an extra-intestinal manifestation (EIM). Epidemiologic and anatomic evidence have demonstrated an intimate crosstalk between the gut and the liver. In this review, we briefly introduced nine groups of susceptibility loci shared by inflammatory bowel and autoimmune liver disease for the first time. The genome-wide association studies (GWAS) evidence of pathways involving crosstalk between the gut and the liver is clarified and explained...
October 21, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27698808/increase-of-t-and-b-cells-and-altered-bach2-expression-patterns-in-bone-marrow-trephines-of-imatinib-treated-patients-with-chronic-myelogenous-leukaemia
#3
Maximilian Von Laffert, Mathias Hänel, Manfred Dietel, Ioannis Anagnostopoulos, Korinna Jöhrens
The effect of imatinib on T and B cells in patients with chronic myelogenous leukaemia (CML) is not well understood. An upregulation of the transcription factor Broad-complex-Tramtrack-Bric-a-Brac and Cap'n'collar 1 bZip transcription factor 2 (BACH2), which is involved in the development and differentiation of B cells, was demonstrated in a CML cell line treated with imatinib. The present study retrospectively analysed the expression and distribution of cluster of differentiation (CD)3, CD20 and BACH2 (per 1,000 cells), as well as the co-expression of CD20 and BACH2, using immunohistochemistry in serial bone marrow trephines obtained from 14 CML patients treated with imatinib in comparison to 17 patients with newly diagnosed CML and 6 control trephines...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27682062/drug-resistant-integrase-mutants-cause-aberrant-hiv-integrations
#4
Janani Varadarajan, Mary Jane McWilliams, Bryan T Mott, Craig J Thomas, Steven J Smith, Stephen H Hughes
BACKGROUND: HIV-1 integrase is the target for three FDA-approved drugs, raltegravir, elvitegravir, and dolutegravir. All three drugs bind at the active site of integrase and block the strand transfer step of integration. We previously showed that sub-optimal doses of the anti-HIV drug raltegravir can cause aberrant HIV integrations that are accompanied by a variety of deletions, duplications, insertions and inversions of the adjacent host sequences. RESULTS: We show here that a second drug, elvitegravir, also causes similar aberrant integrations...
September 29, 2016: Retrovirology
https://www.readbyqxmd.com/read/27680876/a-variant-in-the-bach2-gene-is-associated-with-susceptibility-to-autoimmune-addison-s-disease-in-humans
#5
Agnieszka Pazderska, Bergithe E Oftedal, Catherine M Napier, Holly F Ainsworth, Eystein S Husebye, Heather J Cordell, Simon H S Pearce, Anna L Mitchell
CONTEXT: Autoimmune Addison's disease (AAD) is a rare but highly heritable condition. The BACH2 protein plays a crucial role in T lymphocyte maturation, and allelic variation in its gene has been associated with a number of autoimmune conditions. OBJECTIVE: We aimed to determine whether alleles of the rs3757247 single nucleotide polymorphism (SNP) in the BACH2 gene are associated with AAD. DESIGN, SETTING, AND PATIENTS: This case-control association study was performed in two phases using Taqman chemistry...
November 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27581382/bach2-batf-interactions-control-th2-type-immune-response-by-regulating-the-il-4-amplification-loop
#6
Makoto Kuwahara, Wataru Ise, Mizuki Ochi, Junpei Suzuki, Kohei Kometani, Saho Maruyama, Maya Izumoto, Akira Matsumoto, Nobuaki Takemori, Ayako Takemori, Kenta Shinoda, Toshinori Nakayama, Osamu Ohara, Masaki Yasukawa, Tatsuya Sawasaki, Tomohiro Kurosaki, Masakatsu Yamashita
Although Bach2 has an important role in regulating the Th2-type immune response, the underlying molecular mechanisms remain unclear. We herein demonstrate that Bach2 associates with Batf and binds to the regulatory regions of the Th2 cytokine gene loci. The Bach2-Batf complex antagonizes the recruitment of the Batf-Irf4 complex to AP-1 motifs and suppresses Th2 cytokine production. Furthermore, we find that Bach2 regulates the Batf and Batf3 expressions via two distinct pathways. First, Bach2 suppresses the maintenance of the Batf and Batf3 expression through the inhibition of IL-4 production...
2016: Nature Communications
https://www.readbyqxmd.com/read/27496973/t-cell-fates-zipped-up-how-the-bach2-basic-leucine-zipper-transcriptional-repressor-directs-t-cell-differentiation-and-function
#7
REVIEW
Martin J Richer, Mark L Lang, Noah S Butler
Recent data illustrate a key role for the transcriptional regulator bric-a-brac, tramtrack, and broad complex and cap'n'collar homology (Bach)2 in orchestrating T cell differentiation and function. Although Bach2 has a well-described role in B cell differentiation, emerging data show that Bach2 is a prototypical member of a novel class of transcription factors that regulates transcriptional activity in T cells at super-enhancers, or regions of high transcriptional activity. Accumulating data demonstrate specific roles for Bach2 in favoring regulatory T cell generation, restraining effector T cell differentiation, and potentiating memory T cell development...
August 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27491898/the-intratumoral-balance-between-metabolic-and-immunologic-gene-expression-is-associated-with-anti-pd-1-response-in-patients-with-renal-cell-carcinoma
#8
Maria Libera Ascierto, Tracee L McMiller, Alan E Berger, Ludmila Danilova, Robert A Anders, George J Netto, Haiying Xu, Theresa S Pritchard, Jinshui Fan, Chris Cheadle, Leslie Cope, Charles G Drake, Drew M Pardoll, Janis M Taube, Suzanne L Topalian
Pretreatment tumor PD-L1 expression has been shown to correlate with response to anti-PD-1/PD-L1 therapies. Yet, most patients with PD-L1(+) tumors do not respond to treatment. The current study was undertaken to investigate mechanisms underlying the failure of PD-1-targeted therapies in patients with advanced renal cell carcinoma (RCC) whose tumors express PD-L1. Formalin-fixed, paraffin-embedded pretreatment tumor biopsies expressing PD-L1 were derived from 13 RCC patients. RNA was isolated from PD-L1(+) regions and subjected to whole genome microarray and multiplex quantitative (q)RT-PCR gene expression analysis...
September 2, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27468266/older-age-results-in-differential-gene-expression-after-mild-traumatic-brain-injury-and-is-linked-to-imaging-differences-at-acute-follow-up
#9
Young-Eun Cho, Lawrence L Latour, Hyungsuk Kim, L Christine Turtzo, Anlys Olivera, Whitney S Livingston, Dan Wang, Christiana Martin, Chen Lai, Ann Cashion, Jessica Gill
Older age consistently relates to a lesser ability to fully recover from a traumatic brain injury (TBI); however, there is limited data to explicate the nature of age-related risks. This study was undertaken to determine the relationship of age on gene-activity following a TBI, and how this biomarker relates to changes in neuroimaging findings. A young group (between the ages of 19 and 35 years), and an old group (between the ages of 60 and 89 years) were compared on global gene-activity within 48 h following a TBI, and then at follow-up within 1-week...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27387751/the-double-knockout-of-bach1-and-bach2-in-mice-reveals-shared-compensatory-mechanisms-in-regulating-alveolar-macrophage-function-and-lung-surfactant-homeostasis
#10
Risa Ebina-Shibuya, Miki Watanabe-Matsui, Mitsuyo Matsumoto, Ari Itoh-Nakadai, Ryo Funayama, Keiko Nakayama, Akihiko Muto, Kazuhiko Igarashi
Pulmonary alveolar proteinosis (PAP) is a disease resulting from a dysfunction of the alveolar macrophages (AMs) where excess surfactant protein accumulates in the alveolar spaces. We previously reported that Bach2 KO mice developed PAP due to a defect in the handling of lipids by AMs. To investigate the functions of Bach1 and Bach2, which are regulated by oxidative stress, in the AMs and in lung homeostasis, we generated mice that lacked both Bach1 and Bach2 (Bach1/2 DKO mice). The Bach1/2 DKO mice showed more severe PAP phenotype than Bach2 KO mice with abnormal AMs, whereas the Bach1 KO mice did not develop any pulmonary disease...
December 2016: Journal of Biochemistry
https://www.readbyqxmd.com/read/27327995/bach2-is-required-for-b-cell-and-t-cell-memory-differentiation
#11
Tom Sidwell, Axel Kallies
No abstract text is available yet for this article.
June 21, 2016: Nature Immunology
https://www.readbyqxmd.com/read/27325774/multiple-layers-of-transcriptional-regulation-by-plzf-in-nkt-cell-development
#12
Ai-Ping Mao, Michael G Constantinides, Rebecca Mathew, Zhixiang Zuo, Xiaoting Chen, Matthew T Weirauch, Albert Bendelac
The transcription factor PLZF [promyelocytic leukemia zinc finger, encoded by zinc finger BTB domain containing 16 (Zbtb16)] is induced during the development of innate and innate-like lymphocytes to direct their acquisition of a T-helper effector program, but the molecular mechanisms involved are poorly understood. Using biotinylation-based ChIP-seq and microarray analysis of both natural killer T (NKT) cells and PLZF-transgenic thymocytes, we identified several layers of regulation of the innate-like NKT effector program...
July 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27285766/bach2-promotes-indolent-clinical-presentation-in-waldenstr%C3%A3-m-macroglobulinemia
#13
Charles Herbaux, Elisabeth Bertrand, Guillemette Marot, Christophe Roumier, Nicolas Poret, Valérie Soenen, Olivier Nibourel, Catherine Roche-Lestienne, Natacha Broucqsault, Sylvie Galiègue-Zouitina, Eileen M Boyle, Guillemette Fouquet, Aline Renneville, Sabine Tricot, Franck Morschhauser, Claude Preudhomme, Bruno Quesnel, Stephanie Poulain, Xavier Leleu
Approximately 30% of the patients who fulfil the criteria of Waldenström's macroglobulinemia (WM) are diagnosed while asymptomatic (indolent), and will not require immediate therapy. Conversely, patients with a disease-related event will be considered for therapy. The physiopathology of these 2 groups remains unclear, and the mechanisms of progression from indolent to symptomatic WM have yet to be fully understood. Seventeen patients diagnosed with WM were included in this study, 8 asymptomatic WM (A-WM) and 9 symptomatic WM (S-WM)...
June 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27206783/charge-state-distribution-analysis-of-bach2-intrinsically-disordered-heme-binding-region
#14
Tomoji Suenaga, Miki Watanabe-Matsui, Tamami Uejima, Hiroki Shima, Toshitaka Matsui, Masao Ikeda-Saito, Mikako Shirouzu, Kazuhiko Igarashi, Kazutaka Murayama
Bach2 is a transcriptional repressor that plays an important role in the differentiation of T-cells and B-cells. Bach2 is functionally regulated by heme binding, and possesses five CP-motifs as the heme binding site. To reveal the molecular mechanism of heme binding by Bach2, the intrinsically disordered heme binding region (a.a. 331-520; Bach2(331-520)) and its CP-motif mutant were prepared and characterized with and without heme, by UV-Vis spectroscopy and thermal profiles. In addition, the charge-state-distributions (CSDs) were assessed by electrospray ionization mass spectrometry...
May 20, 2016: Journal of Biochemistry
https://www.readbyqxmd.com/read/27158841/regulated-selection-of-germinal-center-cells-into-the-memory-b-cell-compartment
#15
Ryo Shinnakasu, Takeshi Inoue, Kohei Kometani, Saya Moriyama, Yu Adachi, Manabu Nakayama, Yoshimasa Takahashi, Hidehiro Fukuyama, Takaharu Okada, Tomohiro Kurosaki
Despite the importance of memory B cells in protection from reinfection, how such memory cells are selected and generated during germinal-center (GC) reactions remains unclear. We found here that light-zone (LZ) GC B cells with B cell antigen receptors (BCRs) of lower affinity were prone to enter the memory B cell pool. Mechanistically, cells in this memory-prone fraction had higher expression of the transcriptional repressor Bach2 than that of their counterparts with BCRs of higher affinity. Haploinsufficiency of Bach2 resulted in reduced generation of memory B cells, independently of suppression of the gene encoding the transcription factor Blimp-1...
July 2016: Nature Immunology
https://www.readbyqxmd.com/read/27158840/bach2-regulates-cd8-t-cell-differentiation-by-controlling-access-of-ap-1-factors-to-enhancers
#16
Rahul Roychoudhuri, David Clever, Peng Li, Yoshiyuki Wakabayashi, Kylie M Quinn, Christopher A Klebanoff, Yun Ji, Madhusudhanan Sukumar, Robert L Eil, Zhiya Yu, Rosanne Spolski, Douglas C Palmer, Jenny H Pan, Shashank J Patel, Derek C Macallan, Giulia Fabozzi, Han-Yu Shih, Yuka Kanno, Akihiko Muto, Jun Zhu, Luca Gattinoni, John J O'Shea, Klaus Okkenhaug, Kazuhiko Igarashi, Warren J Leonard, Nicholas P Restifo
T cell antigen receptor (TCR) signaling drives distinct responses depending on the differentiation state and context of CD8(+) T cells. We hypothesized that access of signal-dependent transcription factors (TFs) to enhancers is dynamically regulated to shape transcriptional responses to TCR signaling. We found that the TF BACH2 restrains terminal differentiation to enable generation of long-lived memory cells and protective immunity after viral infection. BACH2 was recruited to enhancers, where it limited expression of TCR-driven genes by attenuating the availability of activator protein-1 (AP-1) sites to Jun family signal-dependent TFs...
July 2016: Nature Immunology
https://www.readbyqxmd.com/read/27058431/small-maf-proteins-maff-mafg-mafk-history-structure-and-function
#17
REVIEW
Fumiki Katsuoka, Masayuki Yamamoto
The small Maf proteins (sMafs) are basic region leucine zipper (bZIP)-type transcription factors. The basic region of the Maf family is unique among the bZIP factors, and it contributes to the distinct DNA-binding mode of this class of proteins. MafF, MafG and MafK are the three vertebrate sMafs, and no functional differences have been observed among them in terms of their bZIP structures. sMafs form homodimers by themselves, and they form heterodimers with cap 'n' collar (CNC) proteins (p45 NF-E2, Nrf1, Nrf2, and Nrf3) and also with Bach proteins (Bach1 and Bach2)...
July 25, 2016: Gene
https://www.readbyqxmd.com/read/27052415/the-bach-family-of-transcription-factors-a-comprehensive-review
#18
REVIEW
Yin Zhou, Haijing Wu, Ming Zhao, Christopher Chang, Qianjin Lu
The transcription factors Bach1 and Bach2, which belong to a basic region-leucine zipper (bZip) family, repress target gene expression by forming heterodimers with small Maf proteins. With the ability to bind to heme, Bach1 and Bach2 are important in maintaining heme homeostasis in response to oxidative stress, which is characterized by high levels of reactive oxygen species (ROS) in cells and thereby induces cellular damage and senescence. The inactivation of Bach1 exerts an antioxidant effect. Thus, Bach1 may be a potential therapeutic target of oxidative stress-related diseases...
June 2016: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/27025005/-extensive-analysis-of-protein-phosphorylation-an-example-of-transcription-factor-bach2
#19
Hiroki Shima, Ryo Ando, Toru Tamahara, Kazuhiko Igarashi
No abstract text is available yet for this article.
February 2016: Seikagaku. the Journal of Japanese Biochemical Society
https://www.readbyqxmd.com/read/26992035/the-spatial-temporal-expression-and-functional-divergence-of-bach-homologs-in-zebrafish-danio-rerio
#20
Q Luo, C Wu, S Sun, F Lu, L Xie, H Zhao, X Zhong, Q Zhou
The spatial-temporal expressions of bach1a, bach1b, bach2a and bach2b in early development of zebrafish Danio rerio embryos were examined in the present study by whole mount in situ hybridization. Transcripts of all genes were found at the one cell stage, suggesting that these four genes are maternally inherited. From the phylogenetic analyses, Bach1a and Bach1b from fishes form a well-supported group with two sub-groups. Bach2a and Bach2b, however, did not fall into one clade, suggesting that Bach2 proteins diverged faster or earlier than Bach1 proteins in fishes...
April 2016: Journal of Fish Biology
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