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Raul Elgueta, Dan Tse, Sophie J Deharvengt, Marcus R Luciano, Catherine Carriere, Randolph J Noelle, Radu V Stan
Plasmalemma vesicle-associated protein (Plvap) is an endothelial protein with roles in endothelial diaphragm formation and maintenance of basal vascular permeability. At the same time, Plvap has roles in immunity by facilitating leukocyte diapedesis at inflammatory sites and controlling peripheral lymph node morphogenesis and the entry of soluble Ags into lymph node conduits. Based on its postulated role in diapedesis, we have investigated the role of Plvap in hematopoiesis and show that deletion of Plvap results in a dramatic decrease of IgM(+)IgD(lo) B cells in both the spleen and the peritoneal cavity...
October 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Cees Bm Oudejans, Ankie Poutsma, Omar J Michel, Hari K Thulluru, Joyce Mulders, Henri J van de Vrugt, Erik A Sistermans, Marie van Dijk
The familial forms of early onset pre-eclampsia and related syndromes (HELLP) present with hypertension and proteinuria in the mother and growth restriction of the fetus. Genetically, these clinically similar entities are caused by different founder-dependent, placentally-expressed paralogous genes. All susceptibility genes (STOX1, lincHELLP, INO80B) identified so far are master control genes that regulate an essential trophoblast differentiation pathway, but act at different entry points. Many genes remain to be identified...
2016: Scientific Reports
Xiaofeng Sun, Dajiang Xiao, Ting Xu, Yuan Yuan
AIM: To investigate the role of miR-24-3p in tumorigenesis and chemosensitivity in head and neck squamous cell carcinoma (HNSCC). METHODS: Growth rate and colony formation assays were performed after transfection with miR-24-3p mimic and inhibitor in cultured SCC-15 cells, followed by a CellTiter-Glo(®) assay. Western blot and luciferase assays were performed to investigate the direct target of miR-24-3p. Xenograft mouse model was used to evaluate combinatorial effects of miR-24-3p inhibitor and 5-fluorouracil...
August 11, 2016: Future Oncology
Alexandra Wille, Thomas Amort, Nicolas Singewald, Simone B Sartori, Alexandra Lusser
Enhanced anxiety is a salient feature of a number of psychiatric disorders including anxiety disorders, trauma-related disorders and depression. Although aberrant expression of various genes has been detected in patients suffering from persistent high anxiety as well as in high anxiety rodent models, the molecular mechanisms responsible for altered transcription regulation have been poorly addressed. Transcription regulation intimately involves the contribution of chromatin modifying processes, such as histone modification and ATP-dependent chromatin remodeling, yet their role in pathological anxiety is not known...
September 15, 2016: Behavioural Brain Research
Zhenfang Du, Lili Li, Xin Huang, Jie Jin, Suming Huang, Qian Zhang, Qian Tao
Renal cell carcinoma (RCC) is the most common urological cancer with steadily increasing incidence. A series of tumor suppressor genes (TSGs) have been identified methylated in RCC as potential epigenetic biomarkers. We identified a 1p36.3 TSG candidate CHD5 as a methylated target in RCC through epigenome study. As the role of CHD5 in RCC pathogenesis remains elusive, we further studied its expression and molecular functions in RCC cells. We found that CHD5 was broadly expressed in most normal genitourinary tissues including kidney, but frequently silenced or downregulated by promoter CpG methylation in 78% of RCC cell lines and 44% (24/55) of primary tumors...
April 19, 2016: Oncotarget
Koumudi Naraparaju, Venkatadri Kolla, Tiangang Zhuang, Mayumi Higashi, Radhika Iyer, Sriharsha Kolla, Erin R Okawa, Gerd A Blobel, Garrett M Brodeur
Neuroblastoma (NB), a tumor of the sympathetic nervous system, is the most common extracranial solid tumor of childhood. We and others have identified distinct patterns of genomic change that underlie diverse clinical behaviors, from spontaneous regression to relentless progression. We first identified CHD5 as a tumor suppressor gene that is frequently deleted in NBs. Mutation of the remaining CHD5 allele is rare in these tumors, yet expression is very low or absent, so expression is likely regulated by epigenetic mechanisms...
March 29, 2016: Oncotarget
Denis Kusevic, Srikanth Kudithipudi, Albert Jeltsch
Bacterial HEMK2 homologs initially had been proposed to be involved in heme biogenesis or to function as adenine DNA methyltransferase. Later it was shown that this family of enzymes has protein glutamine methyltransferase activity, and they methylate the glutamine residue in the GGQ motif of ribosomal translation termination factors. The murine HEMK2 enzyme methylates Gln(185) of the eukaryotic translation termination factor eRF1. We have employed peptide array libraries to investigate the peptide sequence recognition specificity of murine HEMK2...
March 18, 2016: Journal of Biological Chemistry
Alexandra Wille, Verena Maurer, Paolo Piatti, Nigel Whittle, Dietmar Rieder, Nicolas Singewald, Alexandra Lusser
Successful attenuation of fearful memories is a cognitive process requiring initiation of highly coordinated transcription programs. Chromatin-modulating mechanisms such as DNA methylation and histone modifications, including acetylation, are key regulators of these processes. However, knowledge concerning the role of ATP-dependent chromatin remodeling factors (ChRFs) being required for successful fear extinction is lacking. Underscoring the potential importance of these factors that alter histone-DNA contacts within nucleosomes are recent genome-wide association studies linking several ChRFs to various human cognitive and psychiatric disorders...
2015: Frontiers in Behavioral Neuroscience
Song Wu, Zhao Yang, Rui Ye, Dan An, Chong Li, Yitian Wang, Yongqiang Wang, Yi Huang, Huan Liu, Feida Li, Luyun He, Da Sun, Yuan Yu, Qiaoling Li, Peide Huang, Meng Zhang, Xin Zhao, Tengteng Bi, Xuehan Zhuang, Liyan Zhang, Jingxiao Lu, Xiaojuan Sun, Fangjian Zhou, Chunxiao Liu, Guosheng Yang, Yong Hou, Zusen Fan, Zhiming Cai
Bladder cancer (BC) is distinguished by high rate of recurrence after surgery, but the underlying mechanisms remain poorly understood. Here we performed the whole-exome sequencing of 37 BC individuals including 20 primary and 17 recurrent samples in which the primary and recurrent samples were not from the same patient. We uncovered that MLL, EP400, PRDM2, ANK3 and CHD5 exclusively altered in recurrent BCs. Specifically, the recurrent BCs and bladder cancer cells with MLL mutation displayed increased histone H3 tri-methyl K4 (H3K4me3) modification in tissue and cell levels and showed enhanced expression of GATA4 and ETS1 downstream...
January 19, 2016: Oncotarget
Isabelle Westerlund, Ulrika Nyman, Johan Holmberg
No abstract text is available yet for this article.
December 2015: International Journal of Developmental Neuroscience
Masayasu Hayashi, Kazumitsu Maehara, Akihito Harada, Yuichiro Semba, Kensuke Kudo, Hidehisa Takahashi, Shinya Oki, Chikara Meno, Kenji Ichiyanagi, Koichi Akashi, Yasuyuki Ohkawa
Chd5 is an essential factor for neuronal differentiation and spermatogenesis and is a known tumor suppressor. H3K27me3 and H3K4un are modifications recognized by Chd5; however, it remains unclear how Chd5 remodels chromatin structure. We completely disrupted the Chd5 locus using the CRISPR-Cas9 system to generate a 52 kbp long deletion and analyzed Chd5 function in mouse embryonic stem cells. Our findings show that Chd5 represses murine endogenous retrovirus-L (MuERV-L/MERVL), an endogenous retrovirus-derived retrotransposon, by regulating H3K27me3 and H3...
March 2016: Journal of Cellular Biochemistry
Lei Yu, Xuejun Gong, Lei Sun, Hong Yao, Baoling Lu, Liying Zhu
Previous studies showed that miR-454 acted as an oncogene or tumor suppressor in cancer. However, its function in HCC remains unknown. In this study, we found that miR-454 expression was upregulated in HCC cell lines and tissues. Knockdown of miR-454 inhibited HCC cell proliferation and invasion and epithelial mesenchymal transition (EMT), whereas overexpression of miR-454 promoted HCC cell proliferation and invasion and EMT. Furthermore, we identified the CHD5 as a direct target of miR-454. CHD5 was downregulated in HCC tissues and cell lines and the expression level of CHD5 was inversely correlated with the expression of miR-454 in HCC tissues...
November 17, 2015: Oncotarget
Mayumi Higashi, Venkatadri Kolla, Radhika Iyer, Koumudi Naraparaju, Tiangang Zhuang, Sriharsha Kolla, Garrett M Brodeur
BACKGROUND: Chromodomain-helicase DNA binding protein 5 (CHD5) is an important tumor suppressor gene deleted from 1p36.31 in neuroblastomas (NBs). High CHD5 expression is associated with a favorable prognosis, but deletion or low expression is frequent in high-risk tumors. We explored the role of CHD5 expression in the neuronal differentiation of NB cell lines. METHODS: NB cell lines SH-SY5Y (SY5Y), NGP, SK-N-DZ, IMR5, LAN5, SK-N-FI, NB69 and SH-EP were treated with 1-10 μM 13-cis-retinoic acid (13cRA) for 3-12 days...
2015: Molecular Cancer
Alexander Schramm, Johannes Köster, Yassen Assenov, Kristina Althoff, Martin Peifer, Ellen Mahlow, Andrea Odersky, Daniela Beisser, Corinna Ernst, Anton G Henssen, Harald Stephan, Christopher Schröder, Lukas Heukamp, Anne Engesser, Yvonne Kahlert, Jessica Theissen, Barbara Hero, Frederik Roels, Janine Altmüller, Peter Nürnberg, Kathy Astrahantseff, Christian Gloeckner, Katleen De Preter, Christoph Plass, Sangkyun Lee, Holger N Lode, Kai-Oliver Henrich, Moritz Gartlgruber, Frank Speleman, Peter Schmezer, Frank Westermann, Sven Rahmann, Matthias Fischer, Angelika Eggert, Johannes H Schulte
Neuroblastoma is a malignancy of the developing sympathetic nervous system that is often lethal when relapse occurs. We here used whole-exome sequencing, mRNA expression profiling, array CGH and DNA methylation analysis to characterize 16 paired samples at diagnosis and relapse from individuals with neuroblastoma. The mutational burden significantly increased in relapsing tumors, accompanied by altered mutational signatures and reduced subclonal heterogeneity. Global allele frequencies at relapse indicated clonal mutation selection during disease progression...
August 2015: Nature Genetics
Brett Bishop, Kwok Ki Ho, Kim Tyler, Amanda Smith, Sylvia Bonilla, Yuk Fai Leung, Joe Ogas
The chromatin remodeler CHD5 plays a critical role in tumor suppression and neurogenesis in mammals. CHD5 contributes to gene expression during neurogenesis, but there is still much to learn regarding how this class of remodelers contributes to differentiation and development. CHD5 remodelers are vertebrate-specific, raising the prospect that CHD5 plays one or more conserved roles in this phylum. Expression of chd5 in adult fish closely mirrors expression of CHD5 in adult mammals. Knockdown of Chd5 during embryogenesis suggests new roles for CHD5 remodelers based on resulting defects in craniofacial development including reduced head and eye size as well as reduced cartilage formation in the head...
August 2015: Biochimica et Biophysica Acta
Venkatadri Kolla, Koumudi Naraparaju, Tiangang Zhuang, Mayumi Higashi, Sriharsha Kolla, Gerd A Blobel, Garrett M Brodeur
Eukaryotic gene expression is developmentally regulated, in part by chromatin remodelling, and its dysregulation has been linked to cancer. CHD5 (chromodomain helicase DNA-binding protein 5) is a tumour suppressor gene (TSG) that maps to a region of consistent deletion on 1p36.31 in neuroblastomas (NBs) and other tumour types. CHD5 encodes a protein with chromatin remodelling, helicase and DNA-binding motifs that is preferentially expressed in neural and testicular tissues. CHD5 is highly homologous to CHD3 and CHD4, which are the core subunits of nucleosome remodelling and deacetylation (NuRD) complexes...
June 1, 2015: Biochemical Journal
Qin-Liang Fang, Yi-Rui Yin, Cheng-Rong Xie, Sheng Zhang, Wen-Xiu Zhao, Chao Pan, Xiao-Min Wang, Zhen-Yu Yin
Dysregulation of growth factor signaling plays a pivotal role in controlling the malignancy phenotype and progression of hepatocellular carcinoma (HCC). However, the precise oncogenic mechanisms underlying transcription regulation of certain tumor suppressor genes (TSGs) by growth factors are poorly understood. In the present study, we report a novel insulin-like growth factor 1 (IGF1) pathway that mediates de novo DNA methylation and TSG (such as DLC1 and CHD5) silencing by upregulation of the DNA methyltransferase 1 (DNMT1) via an AKT/β-transducin repeat-containing protein (βTrCP)-mediated ubiquitin-proteasome pathway in HCC...
February 2015: International Journal of Oncology
Jinhua Quan, Guillaume Adelmant, Jarrod A Marto, A Thomas Look, Timur Yusufzai
Loss of the chromatin remodeling ATPase CHD5 has been linked to the progression of neuroblastoma tumors, yet the underlying mechanisms behind the tumor suppressor role of CHD5 are unknown. In this study, we purified the human CHD5 complex and found that CHD5 is a component of the full NuRD transcriptional repressor complex, which also contains methyl-CpG binding proteins and histone deacetylases. The CHD5/NuRD complex appears mutually exclusive with the related CHD4/NuRD complex as overexpression of CHD5 results in loss of the CHD4 protein in cells...
2014: PloS One
Shino Shimada, Keiko Shimojima, Nobuhiko Okamoto, Noriko Sangu, Kyoko Hirasawa, Mari Matsuo, Mayo Ikeuchi, Shuichi Shimakawa, Kenji Shimizu, Seiji Mizuno, Masaya Kubota, Masao Adachi, Yoshiaki Saito, Kiyotaka Tomiwa, Kazuhiro Haginoya, Hironao Numabe, Yuko Kako, Ai Hayashi, Haruko Sakamoto, Yoko Hiraki, Koichi Minami, Kiyoshi Takemoto, Kyoko Watanabe, Kiyokuni Miura, Tomohiro Chiyonobu, Tomohiro Kumada, Katsumi Imai, Yoshihiro Maegaki, Satoru Nagata, Kenjiro Kosaki, Tatsuro Izumi, Toshiro Nagai, Toshiyuki Yamamoto
OBJECTIVE: Monosomy 1p36 syndrome is the most commonly observed subtelomeric deletion syndrome. Patients with this syndrome typically have common clinical features, such as intellectual disability, epilepsy, and characteristic craniofacial features. METHOD: In cooperation with academic societies, we analyzed the genomic copy number aberrations using chromosomal microarray testing. Finally, the genotype-phenotype correlation among them was examined. RESULTS: We obtained clinical information of 86 patients who had been diagnosed with chromosomal deletions in the 1p36 region...
May 2015: Brain & Development
Stephen Sojka, Nirav M Amin, Devin Gibbs, Kathleen S Christine, Marta S Charpentier, Frank L Conlon
The identification and characterization of the cellular and molecular pathways involved in the differentiation and morphogenesis of specific cell types of the developing heart are crucial to understanding the process of cardiac development and the pathology associated with human congenital heart disease. Here, we show that the cardiac transcription factor CASTOR (CASZ1) directly interacts with congenital heart disease 5 protein (CHD5), which is also known as tryptophan-rich basic protein (WRB), a gene located on chromosome 21 in the proposed region responsible for congenital heart disease in individuals with Down's syndrome...
August 2014: Development
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