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Mark N Cruickshank, James Dods, Rhonda L Taylor, Mahdad Karimi, Emily J Fenwick, Elizabeth A Quail, Alexander J Rea, V Michael Holers, Lawrence J Abraham, Daniela Ulgiati
Complement receptor 2 (CR2/CD21) plays an important role in the generation of normal B cell immune responses. As transcription appears to be the prime mechanism via which surface CR2/CD21 expression is controlled, understanding transcriptional regulation of this gene will have broader implications to B cell biology. Here we report opposing, cell-context specific control of CR2/CD21 promoter activity by tandem E-box elements, spaced 22 bp apart and within 70 bp of the transcription initiation site. We have identified E2A and USF transcription factors as binding to the distal and proximal E-box sites respectively in CR2-positive B-cells, at a site that is hypersensitive to restriction enzyme digestion compared to non-expressing K562 cells...
July 2015: International Journal of Biochemistry & Cell Biology
X D Kong, N Liu, X J Xu
In this study, biomarkers and transcriptional factor motifs were identified in order to investigate the etiology and phenotypic severity of Down syndrome. GSE 1281, GSE 1611, and GSE 5390 were downloaded from the gene expression ominibus (GEO). A robust multiarray analysis (RMA) algorithm was applied to detect differentially expressed genes (DEGs). In order to screen for biological pathways and to interrogate the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, the database for annotation, visualization, and integrated discovery (DAVID) was used to carry out a gene ontology (GO) function enrichment for DEGs...
October 2014: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Julian Ik-Tsen Heng, Zhengdong Qu, Chiaki Ohtaka-Maruyama, Haruo Okado, Masataka Kasai, Diogo Castro, François Guillemot, Seong-Seng Tan
The zinc finger transcription factor RP58 (also known as ZNF238) regulates neurogenesis of the mouse neocortex and cerebellum (Okado et al. 2009; Xiang et al. 2011; Baubet et al. 2012; Ohtaka-Maruyama et al. 2013), but its mechanism of action remains unclear. In this study, we report a cell-autonomous function for RP58 during the differentiation of embryonic cortical projection neurons via its activities as a transcriptional repressor. Disruption of RP58 expression alters the differentiation of immature neurons and impairs their migration and positioning within the mouse cerebral cortex...
March 2015: Cerebral Cortex
Chiaki Ohtaka-Maruyama, Shinobu Hirai, Akiko Miwa, Julian Ik-Tsen Heng, Hiroshi Shitara, Rie Ishii, Choji Taya, Hitoshi Kawano, Masataka Kasai, Kazunori Nakajima, Haruo Okado
Accumulating evidence suggests that many brain diseases are associated with defects in neuronal migration, suggesting that this step of neurogenesis is critical for brain organization. However, the molecular mechanisms underlying neuronal migration remain largely unknown. Here, we identified the zinc-finger transcriptional repressor RP58 as a key regulator of neuronal migration via multipolar-to-bipolar transition. RP58(-/-) neurons exhibited severe defects in the formation of leading processes and never shifted to the locomotion mode...
February 21, 2013: Cell Reports
Valérie Baubet, Chaomei Xiang, Aliah Molczan, Laura Roccograndi, Svetlana Melamed, Nadia Dahmane
Cerebellum development depends on the correct differentiation of progenitors into neurons, a process controlled by a transcriptional program that remains poorly understood. Here we show that neural-specific deletion of the BTB/POZ zinc-finger transcription factor-encoding gene Rp58 (Znf238, Zfp238) causes severe cerebellar hypoplasia and developmental failure of Purkinje neurons, Bergmann glia and granule neurons. Deletion of Rp58 in mouse embryonic Atoh1(+) progenitors leads to strong defects in growth and foliation owing to its crucial role in the differentiation of granule neurons...
June 2012: Development
Guangai Xue, Yoko Aida, Takashi Onodera, Akikazu Sakudo
Transcription factors regulate gene expression by controlling the transcription rate. Some genes can repress their own expression to prevent over production of the corresponding protein, although the mechanism and significance of this negative feedback regulation remains unclear. In the present study, we describe negative feedback regulation of the bovine prion protein (PrP) gene PRNP in Japanese Black cattle. The PrP-expressing plasmid pEF-boPrP and luciferase-expressing plasmids containing the partial promoter fragment of PRNP incorporating naturally occurring single-nucleotide or insertion/deletion polymorphisms were transfected into N2a cells...
2012: PloS One
Shinobu Hirai, Akiko Miwa, Chiaki Ohtaka-Maruyama, Masataka Kasai, Shigeo Okabe, Yutaka Hata, Haruo Okado
Appropriate number of neurons and glial cells is generated from neural stem cells (NSCs) by the regulation of cell cycle exit and subsequent differentiation. Although the regulatory mechanism remains obscure, Id (inhibitor of differentiation) proteins are known to contribute critically to NSC proliferation by controlling cell cycle. Here, we report that a transcriptional factor, RP58, negatively regulates all four Id genes (Id1-Id4) in developing cerebral cortex. Consistently, Rp58 knockout (KO) mice demonstrated enhanced astrogenesis accompanied with an excess of NSCs...
March 7, 2012: EMBO Journal
C Ohtaka-Maruyama, S Hirai, A Miwa, A Takahashi, H Okado
Pyramidal neurons of the neocortex are produced from progenitor cells located in the neocortical ventricular zone (VZ) and subventricular zone (SVZ) during embryogenesis. RP58 is a transcriptional repressor that is strongly expressed in the developing brain and plays an essential role in corticogenesis. The expression of RP58 is strictly regulated in a time-dependent and spatially restricted manner. It is maximally expressed in E15-16 embryonic cerebral cortex, localized specifically to the cortical plate and SVZ of the neocortex, hippocampus, and parts of amygdala during brain development, and found in glutamatergic but not GABAergic neurons...
January 10, 2012: Neuroscience
C Xiang, V Baubet, S Pal, L Holderbaum, V Tatard, P Jiang, R V Davuluri, N Dahmane
Although neurogenic pathways have been described in the developing neocortex, less is known about mechanisms ensuring correct neuronal differentiation thus also preventing tumor growth. We have shown that RP58 (aka zfp238 or znf238) is highly expressed in differentiating neurons, that its expression is lost or diminished in brain tumors, and that its reintroduction blocks their proliferation. Mice with loss of RP58 die at birth with neocortical defects. Using a novel conditional RP58 allele here we show that its CNS-specific loss yields a novel postnatal phenotype: microencephaly, agenesis of the corpus callosum and cerebellar hypoplasia that resembles the chr1qter deletion microcephaly syndrome in human...
April 2012: Cell Death and Differentiation
Shigetoshi Yokoyama, Hiroshi Asahara
Myogenesis has been a leading model for elucidating the molecular mechanisms that underlie tissue differentiation and development since the discovery of MyoD. During myogenesis, the fate of myogenic precursor cells is first determined by Pax3/Pax7. This is followed by regulation of the myogenic differentiation program by muscle regulatory factors (Myf5, MyoD, Myog, and Mrf4) to form muscle tissues. Recent studies have uncovered a detailed myogenic program that involves the RP58 (Zfp238)-dependent regulatory network, which is critical for repressing the expression of inhibitor of DNA binding (Id) proteins...
June 2011: Cellular and Molecular Life Sciences: CMLS
Shigetoshi Yokoyama, Yoshiaki Ito, Hiroe Ueno-Kudoh, Hirohito Shimizu, Kenta Uchibe, Sonia Albini, Kazuhiko Mitsuoka, Shigeru Miyaki, Minako Kiso, Akane Nagai, Tomohiro Hikata, Tadahiro Osada, Noritsugu Fukuda, Satoshi Yamashita, Daisuke Harada, Valeria Mezzano, Masataka Kasai, Pier Lorenzo Puri, Yoshihide Hayashizaki, Haruo Okado, Megumi Hashimoto, Hiroshi Asahara
We created a whole-mount in situ hybridization (WISH) database, termed EMBRYS, containing expression data of 1520 transcription factors and cofactors expressed in E9.5, E10.5, and E11.5 mouse embryos--a highly dynamic stage of skeletal myogenesis. This approach implicated 43 genes in regulation of embryonic myogenesis, including a transcriptional repressor, the zinc-finger protein RP58 (also known as Zfp238). Knockout and knockdown approaches confirmed an essential role for RP58 in skeletal myogenesis. Cell-based high-throughput transfection screening revealed that RP58 is a direct MyoD target...
December 2009: Developmental Cell
Haruo Okado, Chiaki Ohtaka-Maruyama, Yoshinobu Sugitani, Yuko Fukuda, Reiko Ishida, Shinobu Hirai, Akiko Miwa, Akiyo Takahashi, Katsunori Aoki, Keiji Mochida, Osamu Suzuki, Takao Honda, Kazunori Nakajima, Masaharu Ogawa, Toshio Terashima, Junichiro Matsuda, Hitoshi Kawano, Masataka Kasai
The neocortex and the hippocampus comprise several specific layers containing distinct neurons that originate from progenitors at specific development times, under the control of an adequate cell-division patterning mechanism. Although many molecules are known to regulate this cell-division patterning process, its details are not well understood. Here, we show that, in the developing cerebral cortex, the RP58 transcription repressor protein was expressed both in postmitotic glutamatergic projection neurons and in their progenitor cells, but not in GABAergic interneurons...
July 15, 2009: Developmental Biology
Akiyo Takahashi, Shinobu Hirai, Chiaki Ohtaka-Maruyama, Akiko Miwa, Yutaka Hata, Shigeo Okabe, Haruo Okado
We have cloned a novel transcriptional repressor protein, termed simiRP58, which has high homology to RP58. Both simiRP58 and RP58 belong to the POZ domain and Kruppel Zn finger (POK) family of proteins. Using the luciferase assay system, we found that simiRP58 also has transcriptional repressor activity like RP58. Northern blotting and quantitative RT-PCR showed that simiRP58 was expressed in testes at the highest level. In situ hybridization of testes showed that simiRP58 is expressed by spermatocytes in only a portion of the seminiferous tubules...
April 11, 2008: Biochemical and Biophysical Research Communications
B W Brunelle, M E Kehrli, J R Stabel, D Moody Spurlock, L B Hansen, E M Nicholson
Bovine spongiform encephalopathy (BSE) is a neurodegenerative disease of cattle caused by abnormally folded prion proteins. Two regulatory region polymorphisms in the bovine prion gene are associated with resistance to classical BSE disease: a 23-bp region in the promoter that contains a binding site for the repressor protein RP58, and a 12-bp region in intron 1 that has a binding site for the transcription factor SP1. The presence of these binding sites enhances BSE resistance in cattle, whereas cattle that lack these regions are more susceptible to the disease...
January 2008: Journal of Dairy Science
Chiaki Ohtaka-Maruyama, Akiko Miwa, Hitoshi Kawano, Masataka Kasai, Haruo Okado
RP58, a novel zinc finger protein containing a POZ domain, is a sequence-specific transcriptional repressor. To understand the role of this protein, we examined RP58 gene expression in the developing mouse brain by quantitative polymerase chain reaction (PCR) and in situ hybridization. RP58 mRNA expression was detected at embryonic day (E) 10 in the neuroepithelium, and subsequently in the ventricular zones of the cerebral cortex in the E12 embryo. Strong expression was observed in the preplate in the cerebral cortex from this stage onward...
June 20, 2007: Journal of Comparative Neurology
Petra Sander, Henning Hamann, Cord Drögemüller, Kseniya Kashkevich, Katrin Schiebel, Tosso Leeb
The susceptibility of humans to the variant Creutzfeldt-Jakob disease is greatly influenced by polymorphisms within the human prion protein gene (PRNP). Similar genetic differences exist in sheep, in which PRNP polymorphisms modify the susceptibility to scrapie. However, the known coding polymorphisms within the bovine PRNP gene have little or no effect on bovine spongiform encephalopathy (BSE) susceptibility in cattle. We have recently found a tentative association between PRNP promoter polymorphisms and BSE susceptibility in German cattle (Sander, P...
November 11, 2005: Journal of Biological Chemistry
Mitsuo Sakamoto, Yi Huang, Makoto Umeda, Isao Ishikawa, Yoshimi Benno
A phylogenetic approach based on 16S rRNA (rDNA) has been recently applied to investigate the diversity of cultivable and uncultivable species in the human oral cavity without cultivation. In a previous study [Sakamoto et al. (2000) Microbiol. Immunol. 44, 643-652], we identified a number of novel oral phylotypes, representing as yet uncultured organisms. The purpose of this study was to design specific PCR primers for five phylotypes AP12, AP21, AP24, AP50, and RP58, which are deeply branched particularly in the phylogenetic tree, and determine the prevalence of these phylotypes in 45 patients with periodontitis and 18 healthy subjects...
November 19, 2002: FEMS Microbiology Letters
Jian-Sheng Kang, Yong-Chen Yang, Hai-Lan Liu, Yong-Hong Li, Yu-Cang Du, Rong-Xiu Li
EST (AW055733) is a 3'-cDNA fragment specially expressed in rat brain. It is homologous to human and mouse RP58 gene, which is a transcriptional repressor gene. Primers were designed based on these two genes, and then two transcripts of rRP58 gene were got from male SD rat using RT-PCR method. The rRP58 protein is a C(2)H(2) type zinc finger protein, containing POZ domain at N-terminal and zinc finger domain (ZFD) at C-terminal. In addition, there is a highly acidic region between POZ and ZFD. POZ and ZFD were cloned, expressed and purified...
2001: Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao Acta Biochimica et Biophysica Sinica
F Fuks, W A Burgers, N Godin, M Kasai, T Kouzarides
The Dnmt3a DNA methyltransferase is essential for mammalian development and is responsible for the generation of genomic methylation patterns, which lead to transcriptional silencing. Here, we show that Dnmt3a associates with RP58, a DNA-binding transcriptional repressor protein found at transcriptionally silent heterochromatin. Dnmt3a acts as a co-repressor for RP58 in a manner that does not require its de novo methyltransferase activity. Like other characterized co-repressors, Dnmt3a associates with the histone deacetylase HDAC1 using its ATRX-homology domain...
May 15, 2001: EMBO Journal
G Meng, J Inazawa, R Ishida, K Tokura, K Nakahara, K Aoki, M Kasai
RP58, a sequence-specific transcriptional repressor sharing homology with the POZ domain of a number of zinc-finger proteins, is highly synthesized in brain and localized in condensed chromatin regions, suggesting a role in transcriptional repression in the central nervous system. In the present study, genomic clones of the human rp58 gene were isolated to determine the complete genomic organization. Sequence analyses indicated that the human rp58 gene encoding the functional protein is uninterrupted over its entire 4...
January 25, 2000: Gene
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