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Yurina Shishido, Takashi Baba, Tetsuya Sato, Yuichi Shima, Kanako Miyabayashi, Miki Inoue, Haruhiko Akiyama, Hiroshi Kimura, Yoshiakira Kanai, Yasuhiro Ishihara, Shogo Haraguchi, Akira Miyazaki, Damjana Rozman, Takeshi Yamazaki, Man-Ho Choi, Yasuyuki Ohkawa, Mikita Suyama, Ken-Ichirou Morohashi
SRY, a sex-determining gene, induces testis development in chromosomally female (XX) individuals. However, mouse XX Sertoli cells carrying Sry (XX/Sry Sertoli cells) are incapable of fully supporting germ cell development, even when the karyotype of the germ cells is XY. While it has therefore been assumed that XX/Sry Sertoli cells are not functionally equivalent to XY Sertoli cells, it has remained unclear which specific functions are affected. To elucidate the functional difference, we compared the gene expression of XY and XX/Sry Sertoli cells...
February 2, 2017: Scientific Reports
Yunhui Peng, Emil Alexov
The KDM5C gene (also known as JARID1C and SMCX) is located on the X chromosome and encodes a ubiquitously expressed 1560-aa protein, which plays an important role in lysine methylation (specifically reverses tri- and di-methylation of Lys4 of histone H3). Currently, 13 missense mutations in KDM5C have been linked to X-linked mental retardation. However, the molecular mechanism of disease is currently unknown due to the experimental difficulties in expressing such large protein and the lack of experimental 3D structure...
December 2016: Proteins
Jelena Ciric, Katarina Lazic, Jelena Petrovic, Aleksandar Kalauzi, Jasna Saponjic
We followed the impact of healthy aging on cortical drive during sleep in rats by using the corticomuscular coherence (CMC). We employed the chronic electrodes implantation for sleep recording in adult, male Wistar rats, and followed the aging impact during sleep from 3 to 5.5 months age. We have analyzed the sleep/wake states architecture, and the sleep/wake state related EEG microstructure and CMCs. We evidenced the topographically distinct impact of aging on sleep/wake states architecture within the sensorimotor (SMCx) vs...
March 2015: Mechanisms of Ageing and Development
Liuping Zhang, Jie Wang, Yaoqian Pan, Jie Jin, Jianrong Sang, Pan Huang, Genbao Shao
Histone H3 lysine 4 methylation (H3K4me) is an epigenetic modification associated with gene activation and is dynamically regulated by histone methylases and demethylases. To date, the expression patterns of H3K4me and its demethylases in the developing testis remain unclear. The present study was designed to detect the expression of H3K4me1/2/3 and its demethylases LSD1, RBP2 and SMCX in 21-, 40- and 60-day-old mouse testes by using immunohistochemistry, quantitative real-time polymerase chain reaction (PCR) and Western blot...
December 2014: Cell and Tissue Research
Jennifer A Smith, Friederike S Haberstroh, Elizabeth A White, David M Livingston, James A DeCaprio, Peter M Howley
An important step in the malignant progression of HPV-associated lesions is the dysregulation of expression of the viral E6 and E7 oncogenes. This is often achieved through the loss of expression of E2, which represses the HPV LCR promoter and E6/E7 expression. Our previous studies confirmed a role for Brd4 in mediating the E2 transcriptional repression function, and identified JARID1C/SMCX and EP400 as contributors to E2-mediated repression. Here we show that TIP60, a component of the TIP60/TRRAP histone acetyltransferase complex, also contributes to the E2 repression function, and we extend our studies on SMCX...
November 2014: Virology
Jelena Petrovic, Katarina Lazic, Aleksandar Kalauzi, Jasna Saponjic
The aim of this study was to demonstrate that two REM clusters, which emerge following bilateral pedunculopontine tegmental nucleus (PPT) lesions in rats, are two functionally distinct REM states. We performed the experiments in Wistar rats, chronically instrumented for sleep recording. Bilateral PPT lesions were produced by the microinfusion of 100 nl of 0.1M ibotenic acid (IBO). Following a recovery period of 2 weeks, we recorded their sleep for 6h. Bilateral PPT lesions were identified by NADPH - diaphorase histochemistry...
September 1, 2014: Behavioural Brain Research
Malini Vashishtha, Christopher W Ng, Ferah Yildirim, Theresa A Gipson, Ian H Kratter, Laszlo Bodai, Wan Song, Alice Lau, Adam Labadorf, Annie Vogel-Ciernia, Juan Troncosco, Christopher A Ross, Gillian P Bates, Dimitri Krainc, Ghazaleh Sadri-Vakili, Steven Finkbeiner, J Lawrence Marsh, David E Housman, Ernest Fraenkel, Leslie M Thompson
Transcriptional dysregulation is an early feature of Huntington disease (HD). We observed gene-specific changes in histone H3 lysine 4 trimethylation (H3K4me3) at transcriptionally repressed promoters in R6/2 mouse and human HD brain. Genome-wide analysis showed a chromatin signature for this mark. Reducing the levels of the H3K4 demethylase SMCX/Jarid1c in primary neurons reversed down-regulation of key neuronal genes caused by mutant Huntingtin expression. Finally, reduction of SMCX/Jarid1c in primary neurons from BACHD mice or the single Jarid1 in a Drosophila HD model was protective...
August 6, 2013: Proceedings of the National Academy of Sciences of the United States of America
Nikolay S Outchkourov, Jose M Muiño, Kerstin Kaufmann, Wilfred F J van Ijcken, Marian J Groot Koerkamp, Dik van Leenen, Petra de Graaf, Frank C P Holstege, Frank G Grosveld, H T Marc Timmers
The functional organization of eukaryotic genomes correlates with specific patterns of histone methylations. Regulatory regions in genomes such as enhancers and promoters differ in their extent of methylation of histone H3 at lysine-4 (H3K4), but it is largely unknown how the different methylation states are specified and controlled. Here, we show that the Kdm5c/Jarid1c/SMCX member of the Kdm5 family of H3K4 demethylases can be recruited to both enhancer and promoter elements in mouse embryonic stem cells and in neuronal progenitor cells...
April 25, 2013: Cell Reports
Cheng Liu, Dawei Xu, Hongya Han, Yidong Fan, Frida Schain, Zhonghua Xu, Hans-Erik Claesson, Magnus Björkholm, Jan Sjöberg
15-Lipoxygenase-1 (15-LOX-1) oxidizes polyunsaturated fatty acids to a rich spectrum of biologically active metabolites and is implicated in physiological membrane remodelling, inflammation and apoptosis. Its deregulation is involved in the pathogenesis of diverse cancer and immune diseases. Recent experimental evidence reveals that dynamic histone methylation/demethylation mediated by histone methyltransferases and demethylases plays a critical role in regulation of chromatin remodelling and gene expression...
2012: PloS One
Yukako Katsura, Yoko Satta
Mammalian sex chromosomes originated from a pair of autosomes, and homologous genes on the sex chromosomes (gametologs) differentiated through recombination arrest between the chromosomes. It was hypothesized that this differentiation in eutherians took place in a stepwise fashion and left a footprint on the X chromosome termed "evolutionary strata." The evolutionary stratum hypothesis claims that strata 1 and 2 (which correspond to the first two steps of chromosomal differentiation) were generated in the stem lineage of Theria or before the divergence between eutherians and marsupials...
2012: PloS One
Yan Li, Tan Tan, Le Zong, Dacheng He, Wei Tao, Qianjin Liang
Histone methylation is one epigenetic modification of an inactive X chromosome (Xi). Histone H3 lysine 9 dimethylation (H3K9me) and histone H3 lysine 27 trimethylation (H3K27me) are both associated with the chromatin of gene-silenced regions in the X chromosome and with X inactivation. Studies have shown that H3K9me is supposedly an early mark on the X chromosome during inactivation. Here, we examined the distribution and enrichment profiles of H3K9me and H3K27me by indirect immunofluorescence. We found that H3K9me appears to have a broad distribution throughout the whole genome, but is specific, to a certain extent, to the Xi in WI38 cells...
August 2012: Chromosome Research
Wenying Meng, Zhimou Guo, Weijian Shen, Chongyu Shen, Bin Wu, Yanming Liu, Feifang Zhang, Xinmiao Liang
A simple and efficient method based on a novel solid phase extraction (SPE) cartridge and ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/ MS) was developed for the determination of clenbuterol residue in pork. The minced pork sample was ultrasonically extracted by 5% (v/v) perchloric acid and centrifuged at 10 000 r/min for 15 min, then the supernatant was purified by an SMCX cartridge, which is a novel SPE column based on homemade silica matrix with two mixed modes of reversed-phase and strong cation exchange, for the selective enrichment and purification of the analyte...
February 2012: Se Pu, Chinese Journal of Chromatography
R J Simensen, R C Rogers, J S Collins, F Abidi, C E Schwartz, R E Stevenson
We present the cognitive abilities of females from five families who carry a mutation in a gene (KDM5C, formerly JARIDIC or SMCX) in Xp 11.2 that encodes a transcriptional regulator with histone demethylase activity that is specific for dimethylated and trimethylated H3K4. In this report, the cognitive abilities of females who carry KDMSC mutations are compared to females who carry mutations in other genes known to cause X-linked intellectual and developmental disability (XLIDD) conditions. The KDM5C mutation carriers had higher mean scores on the abstract/visual and quantitative sections of the Stanford-Binet Intelligence Scale: Fourth Edition and lower mean short term memory scores...
2012: Genetic Counseling
Po-Hsien Huang, Christoph Plass, Ching-Shih Chen
A recent study reports that histone deacetylase (HDAC) inhibitors, AR42 and MS- 275, upregulated H3K4 methylation marks in prostate cancer cells, leading to transcriptional activation of genes including those associated with roles in tumor suppression and cell differentiation (1). Evidence suggests that the crosstalk between histone deacetylation and histone H3K4 methylation is attributable to the ability of these HDAC inhibitors to repress the JARID1 family of histone H3 lysine 4 demethylases (H3K4DMs), including RBP2, PLU-1, SMCX, and LSD1, through the downregulation of Sp1 expression...
2011: Molecular and Cellular Pharmacology
Katrin Ounap, Helen Puusepp-Benazzouz, Maire Peters, Ulvi Vaher, Reet Rein, Anne Proos, Mike Field, Tiia Reimand
Mutations in the KDM5C gene (lysine (K)-specific demethylase 5C gene; also known as JARID1C and SMCX; MIM 314690) were recently associated with X-linked intellectual disability (XLID). To date only two case reports and five studies that screen for mutations in the KDM5C gene have been published, with 21 mutations reported. Herein we present a large family with XLID caused by a novel mutation c.2T > C in the start codon of the KDM5C gene, presumably leading to loss of gene translation. Six sibs out of seven (two sons and four sisters) and their mother carry this mutation...
March 2012: European Journal of Medical Genetics
Zhihui Liang, Marc Diamond, Johanna A Smith, Matthias Schnell, René Daniel
BACKGROUND: Histone methylation is regulated by a large number of histone methyltransferases and demethylases. The recently discovered SMCX/KMD5C demethylase has been shown to remove methyl residues from lysine 4 of histone H3 (H3K4), and constitutes an important component of the regulatory element-1-silencing transcription factor (REST) protein complex. However, little is known about the cellular mechanisms that control SMCX activity and intracellular trafficking. RESULTS: In this study, we found that small interfering RNA-mediated knockdown of proliferating cell nuclear antigen (PCNA) resulted in the reduction of the chromatin-bound SMCX fraction...
2011: Epigenetics & Chromatin
X Niu, T Zhang, L Liao, L Zhou, D J Lindner, M Zhou, B Rini, Q Yan, H Yang
In clear-cell renal cell carcinoma (ccRCC), inactivation of the tumor suppressor von Hippel-Lindau (VHL) occurs in the majority of the tumors and is causal for the pathogenesis of ccRCC. Recently, a large-scale genomic sequencing study of ccRCC tumors revealed that enzymes that regulate histone H3 lysine 4 trimethylation (H3K4Me3), such as JARID1C/KDM5C/SMCX and MLL2, were mutated in ccRCC tumors, suggesting that H3K4Me3 might have an important role in regulating gene expression and tumorigenesis. In this study we report that in VHL-deficient ccRCC cells, the overall H3K4Me3 levels were significantly lower than that of VHL+/+ counterparts...
February 9, 2012: Oncogene
Cíntia B Santos-Rebouças, Natalia Fintelman-Rodrigues, Lars R Jensen, Andreas W Kuss, Márcia G Ribeiro, Mário Campos, Jussara M Santos, Márcia M G Pimentel
Mutations in the Jumonji AT-rich interactive domain 1C (JARID1C/SMCX/KDM5C) gene, located at Xp11.22, are emerging as frequent causes of X-linked intellectual disability (XLID). KDM5C encodes for a member of an ARID protein family that harbors conserved DNA-binding motifs and acts as a histone H3 lysine 4 demethylase, suggesting a potential role in epigenetic regulation during development, cell growth and differentiation. In this study, we describe clinical and genetic findings of a Brazilian family co-segregating a novel nonsense mutation (c...
July 1, 2011: Neuroscience Letters
Po-Hsien Huang, Chun-Han Chen, Chih-Chien Chou, Aaron M Sargeant, Samuel K Kulp, Che-Ming Teng, John C Byrd, Ching-Shih Chen
This study investigates the mechanism by which histone deacetylase (HDAC) inhibitors up-regulate histone H3 lysine 4 (H3K4) methylation. Exposure of LNCaP prostate cancer cells and the prostate tissue of transgenic adenocarcinoma of the mouse prostate mice to the pan- and class I HDAC inhibitors (S)-(+)-N-hydroxy-4-(3-methyl-2-phenyl-butyrylamino)-benzamide (AR42), N-(2-aminophenyl)-4-[N-(pyridine-3-yl-methoxycarbonyl)-aminomethyl]-benzamide (MS-275), and vorinostat led to differential increases in H3K4 methylation...
January 2011: Molecular Pharmacology
Fu Huang, Mahesh B Chandrasekharan, Yi-Chun Chen, Srividya Bhaskara, Scott W Hiebert, Zu-Wen Sun
Histone lysine methylation is a dynamic process that plays an important role in regulating chromatin structure and gene expression. Recent studies have identified Jhd2, a JmjC domain-containing protein, as an H3K4-specific demethylase in budding yeast. However, important questions regarding the regulation and functions of Jhd2 remain unanswered. In this study, we show that Jhd2 has intrinsic activity to remove all three states of H3K4 methylation in vivo and can dynamically associate with chromatin to modulate H3K4 methylation levels on both active and repressed genes and at the telomeric regions...
August 6, 2010: Journal of Biological Chemistry
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