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Can Zhu, Ge Chen, Ying Zhao, Xiao-Ming Gao, Jun Wang
The large ZBTB family comprises a diverse group of transcriptional factors. Several ZBTB proteins have emerged as critical factors that regulate the lineage commitment, differentiation, and function of lymphoid cells as well as many other developmental events. For instance, dysfunctions of ZBTB20 or ZBTB24 have been linked to multisystem failures in humans. Within the B-cell lineage, BCL6, ZBTB7A, ZBTB17, and ZBTB1 regulate the development/differentiation of B cells in both bone marrow and peripheral lymphoid organs, while ZBTB20 and ZBTB32 seem to mainly impact the maintenance of terminal plasma cells...
2018: Frontiers in Immunology
Maryam Baazm, Farideh Jalali Mashayekhi, Saeid Babaie, Parvindokht Bayat, Cordian Beyer, Adib Zendedel
Spermatongonial stem cells (SSCs) are unique testis cells that are able to proliferate, differentiate, and transmit genetic information to the next generation. However, the effect of different Sertoli cell types on the expression of specific SSC genes is not yet well understood. In this study, we compare the in vitro effect of adult Sertoli cells, embryonic Sertoli cells, and TM4 (a Sertoli cell line) as feeder layers on the expression of SSC genes. SSCs were isolated from the testis of adult male mice and purified by differential plating...
September 2017: In Vitro Cellular & Developmental Biology. Animal
Liang Xu, Ye Chen, Marina Dutra-Clarke, Anand Mayakonda, Masaharu Hazawa, Steve E Savinoff, Ngan Doan, Jonathan W Said, William H Yong, Ashley Watkins, Henry Yang, Ling-Wen Ding, Yan-Yi Jiang, Jeffrey W Tyner, Jianhong Ching, Jean-Paul Kovalik, Vikas Madan, Shing-Leng Chan, Markus Müschen, Joshua J Breunig, De-Chen Lin, H Phillip Koeffler
ZBTB transcription factors orchestrate gene transcription during tissue development. However, their roles in glioblastoma (GBM) remain unexplored. Here, through a functional screening of ZBTB genes, we identify that BCL6 is required for GBM cell viability and that BCL6 overexpression is associated with worse prognosis. In a somatic transgenic mouse model, depletion of Bcl6 inhibits the progression of KrasG12V-driven high-grade glioma. Transcriptome analysis demonstrates the involvement of BCL6 in tumor protein p53 (TP53), erythroblastic leukemia viral oncogene homolog (ErbB), and MAPK signaling pathways...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
K Burrows, F Antignano, M Bramhall, A Chenery, S Scheer, V Korinek, T M Underhill, C Zaph
The intestine is a unique immune environment that must respond to infectious organisms but remain tolerant to commensal microbes and food antigens. However, the molecular mechanisms that regulate immune cell function in the intestine remain unclear. Here we identify the POK/ZBTB family transcription factor hypermethylated in cancer 1 (HIC1, ZBTB29) as a central component of immunity and inflammation in the intestine. HIC1 is specifically expressed in immune cells in the intestinal lamina propria (LP) in the steady state and mice with a T-cell-specific deletion of HIC1 have reduced numbers of T cells in the LP...
November 2017: Mucosal Immunology
Takahiro Maeda
No abstract text is available yet for this article.
July 22, 2016: International Journal of Hematology
Ye Seul Bae, Sun-Wha Im, Mi So Kang, Jin Hee Kim, Soon Hang Lee, Be Long Cho, Jin Ho Park, You-Seon Nam, Ho-Young Son, San Deok Yang, Joohon Sung, Kwang Ho Oh, Jae Moon Yun, Jong Il Kim
Osteoporosis is a medical condition of global concern, with increasing incidence in both sexes. Bone mineral density (BMD), a highly heritable trait, has been proven a useful diagnostic factor in predicting fracture. Because medical information is lacking about male osteoporotic genetics, we conducted a genome-wide association study of BMD in Korean men. With 1,176 participants, we analyzed 4,414,664 single nucleotide polymorphisms (SNPs) after genomic imputation, and identified five SNPs and three loci correlated with bone density and strength...
June 2016: Genomics & Informatics
Takahiro Maeda
Hematopoietic development is governed by the coordinated expression of lineage- and differentiation stage-specific genes. Transcription factors play major roles in this process and their perturbation may underlie hematologic and immunologic disorders. Nearly 1900 transcription factors are encoded in the human genome: of these, 49 BTB (for broad-complex, tram-track and bric à brac)-zinc finger transcription factors referred to as ZBTB or POK proteins have been identified. ZBTB proteins, including BCL6, PLZF, ThPOK and LRF, exhibit a broad spectrum of functions in normal and malignant hematopoiesis...
September 2016: International Journal of Hematology
J Liang, R Yan, G Chen, J Feng, W-W Wu, W Ren, C Zhu, Y Zhao, X-M Gao, J Wang
It has been recently identified that loss-of-function mutations in the uncharacterized gene ZBTB24 (zinc finger and BTB domain-containing 24) cause ICF2 (immunodeficiency, centromeric instability and facial anomalies syndrome 2) with immunological characteristics of greatly reduced serum antibodies and circulating memory B cells. ZBTB24 belongs to the large ZBTB family of transcriptional repressors with members like B-cell lymphoma 6 (BCL-6; ZBTB27) playing critical roles in B-cell functions. Given the genotype-phenotype correlation analyses in ICF2 patients and the high expression of ZBTB24 in human B cells, we, in the present study, investigated the function of ZBTB24 in human B-cell line Raji cells...
July 2016: Genes and Immunity
David R Rocha, Jorge André M Martins, Mauricio F van Tilburg, Rodrigo V Oliveira, Frederico B Moreno, Ana Cristina O Monteiro-Moreira, Renato A Moreira, Airton A Araújo, Arlindo A Moura
The present study evaluated the effects of heat stress on the ram seminal plasma proteome. Six Morada Nova rams were scrotal insulated for 8 days. Scrotal circumference, sperm parameters, and seminal fluid proteins were evaluated before (Day 0) and twice during scrotal insulation (Days 4 and 8), and weekly until semen parameters returned to preinsulation values (normal). Seminal proteins were analyzed by two-dimensional SDS-PAGE and mass spectrometry. Scrotal circumference decreased from 30 ± 0.4 cm on Day 0 to 22...
November 2015: Theriogenology
Indira Jutooru, Aaron S Guthrie, Gayathri Chadalapaka, Satya Pathi, KyoungHyun Kim, Robert Burghardt, Un-Ho Jin, Stephen Safe
Reactive oxygen species (ROS)-inducing anticancer agents such as phenethylisothiocyanate (PEITC) activate stress pathways for killing cancer cells. Here we demonstrate that PEITC-induced ROS decreased expression of microRNA 27a (miR-27a)/miR-20a:miR-17-5p and induced miR-regulated ZBTB10/ZBTB4 and ZBTB34 transcriptional repressors, which, in turn, downregulate specificity protein (Sp) transcription factors (TFs) Sp1, Sp3, and Sp4 in pancreatic cancer cells. Decreased expression of miR-27a/miR-20a:miR-17-5p by PEITC-induced ROS is a key step in triggering the miR-ZBTB Sp cascade leading to downregulation of Sp TFs, and this is due to ROS-dependent epigenetic effects associated with genome-wide shifts in repressor complexes, resulting in decreased expression of Myc and the Myc-regulated miRs...
July 2014: Molecular and Cellular Biology
Andrea Lunardi, Jlenia Guarnerio, Guocan Wang, Takahiro Maeda, Pier Paolo Pandolfi
In the human genome, 43 different genes are found that encode proteins belonging to the family of the POK (poxvirus and zinc finger and Krüppel)/ZBTB (zinc finger and broad complex, tramtrack, and bric à brac) factors. Generally considered transcriptional repressors, several of these genes play fundamental roles in cell lineage fate decision in various tissues, programming specific tasks throughout the life of the organism. Here, we focus on functions of leukemia/lymphoma-related factor/POK erythroid myeloid ontogenic factor, which is probably one of the most exciting and yet enigmatic members of the POK/ZBTB family...
April 11, 2013: Blood
Caitlyn W Barrett, J Joshua Smith, Lauren C Lu, Nicholas Markham, Kristy R Stengel, Sarah P Short, Baolin Zhang, Aubrey A Hunt, Barbara M Fingleton, Robert H Carnahan, Michael E Engel, Xi Chen, R Daniel Beauchamp, Keith T Wilson, Scott W Hiebert, Albert B Reynolds, Christopher S Williams
Myeloid translocation genes (MTGs) are transcriptional corepressors originally identified in acute myelogenous leukemia that have recently been linked to epithelial malignancy with non-synonymous mutations identified in both MTG8 and MTG16 in colon, breast, and lung carcinoma in addition to functioning as negative regulators of WNT and Notch signaling. A yeast two-hybrid approach was used to discover novel MTG binding partners. This screen identified the Zinc fingers, C2H2 and BTB domain containing (ZBTB) family members ZBTB4 and ZBTB38 as MTG16 interacting proteins...
2012: PloS One
Stéphane Gérart, Sophie Sibéril, Emmanuel Martin, Christelle Lenoir, Claire Aguilar, Capucine Picard, Olivier Lantz, Alain Fischer, Sylvain Latour
Invariant natural killer (iNKT) T cells and mucosal-associated invariant T (MAIT) cells represent peculiar T-lymphocyte subpopulations with innate-like properties that differ from conventional T cells. iNKT are reduced in the primary immunodeficiency caused by mutations in the X-linked inhibitor of apoptosis (XIAP). By studying the mechanism of this depletion, we herein report that iNKT cells exhibit a high susceptibility to apoptosis that is not observed with conventional T cells. Elevated expression of caspases 3 and 7 accounts for the proapoptotic phenotype of iNKT cells, which is inhibited by XIAP although it exerts a moderate effect in conventional T cells...
January 24, 2013: Blood
Sung-Uk Lee, Takahiro Maeda
The germinal center (GC) is a unique histological structure found in peripheral lymphoid organs. GCs provide an important source of humoral immunity by generating high affinity antibodies against a pathogen. The GC response is tightly regulated during clonal expansion, immunoglobulin modification, and affinity maturation, whereas its deregulation has a detrimental effect on immune function, leading to development of diseases, such as lymphoma and autoimmunity. LRF (lymphoma/leukemia-related factor), encoded by the ZBTB7A gene, is a transcriptional repressor belonging to the POK (POZ and Krüppel)/ZBTB (zing finger and BTB) protein family...
May 2012: Immunological Reviews
Hong Zhang, Margaux A Morrison, Andy Dewan, Scott Adams, Michael Andreoli, Nancy Huynh, Maureen Regan, Alison Brown, Joan W Miller, Ivana K Kim, Josephine Hoh, Margaret M Deangelis
BACKGROUND: To examine if the significantly associated SNPs derived from the genome wide allelic association study on the AREDS cohort at the NEI (dbGAP) specifically confer risk for neovascular age-related macular degeneration (AMD). We ascertained 134 unrelated patients with AMD who had one sibling with an AREDS classification 1 or less and was past the age at which the affected sibling was diagnosed (268 subjects). Genotyping was performed by both direct sequencing and Sequenom iPLEX system technology...
June 9, 2008: BMC Medical Genetics
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