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Bhavana Muralidharan, Zeba Khatri, Upasana Maheshwari, Ritika Gupta, Basabdatta Roy, Saurabh J Pradhan, Krishanpal Karmodiya, Hari Padmanabhan, Ashwin Shetty, Chinthapalli Balaji, Ullas Kolthur-Seetharam, Jeffrey D Macklis, Sanjeev Galande, Shubha Tole
: In the developing cerebral cortex, sequential transcriptional programs take neuroepithelial cells from proliferating progenitors to differentiated neurons with unique molecular identities. The regulatory changes that occur in the chromatin of the progenitors are not well understood. During deep layer neurogenesis, we show that transcription factor Lhx2 binds to distal regulatory elements of Fezf2 and Sox11, critical determinants of neuron subtype identity in the mouse neocortex. We demonstrate that Lhx2 binds to the NuRD histone remodeling complex subunits LSD1, HDAC2, and RBBP4, which are proximal regulators of the epigenetic state of chromatin...
December 1, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Xiaolu Wang, Feng Yao, Xiaoyu Liang, Xiaolin Zhu, Ren Zheng, Baolin Jia, Lin Hou, Xiangyang Zou
Retinoblastoma binding protein 4 (RBBP4) is a nuclear protein with four WD-repeat sequences and thus belongs to a highly conserved subfamily of proteins with such domains. This retinoblastoma-binding protein plays an important role in nucleosome assembly and histone modification, which influences gene transcription and regulates cell cycle and proliferation. Artemia sinica (brine shrimp) undergoes an unusual diapause process under stress conditions of high salinity and low temperature. However, the role of RBBP4 in diapause termination of embryo development in A...
October 15, 2016: Gene
Jason W Schmidberger, Mehdi Sharifi Tabar, Mario Torrado, Ana P G Silva, Michael J Landsberg, Lou Brillault, Saad AlQarni, Yi Cheng Zeng, Benjamin L Parker, Jason K K Low, Joel P Mackay
The nucleosome remodeling and deacetylase (NuRD) complex remodels the genome in the context of both gene transcription and DNA damage repair. It is essential for normal development and is distributed across multiple tissues in organisms ranging from mammals to nematode worms. In common with other chromatin-remodeling complexes, however, its molecular mechanism of action is not well understood and only limited structural information is available to show how the complex is assembled. As a step towards understanding the structure of the NuRD complex, we have characterized the interaction between two subunits: the metastasis associated protein MTA1 and the histone-binding protein RBBP4...
August 2016: Protein Science: a Publication of the Protein Society
Christopher J Millard, Niranjan Varma, Almutasem Saleh, Kyle Morris, Peter J Watson, Andrew R Bottrill, Louise Fairall, Corinne J Smith, John W R Schwabe
The NuRD complex is a multi-protein transcriptional corepressor that couples histone deacetylase and ATP-dependent chromatin remodelling activities. The complex regulates the higher-order structure of chromatin, and has important roles in the regulation of gene expression, DNA damage repair and cell differentiation. HDACs 1 and 2 are recruited by the MTA1 corepressor to form the catalytic core of the complex. The histone chaperone protein RBBP4, has previously been shown to bind to the carboxy-terminal tail of MTA1...
April 21, 2016: ELife
Fengjie Cui, Xinyi Zan, Yunhong Li, Wenjing Sun, Yan Yang, Lifeng Ping
GFG-3a is a novel glycoprotein previously purified from the fermented mycelia of Grifola frondosa with novel sugar compositions and protein sequencing. The present study aims to investigate its effects on the cell cycle, differential proteins expression, and apoptosis of human gastric cancer SGC-7901 cells. Our findings revealed that GFG-3a induced the cell apoptosis and arrested cell cycle at S phase. GFG-3a treatment resulted in the differential expression of 21 proteins in SGC-7901 cells by upregulating 10 proteins including RBBP4 associated with cell cycle arrest and downregulating 11 proteins including RUVBL1, NPM, HSP90AB1, and GRP78 involved in apoptosis and stress response...
2016: Nutrition and Cancer
Christine Sattler, Beatrix Steer, Heiko Adler
An unresolved question in herpesvirus biology is why some herpesviruses contain more than one lytic origin of replication (oriLyt). Using murine gammaherpesvirus 68 (MHV-68) as model virus containing two oriLyts, we demonstrate that loss of either of the two oriLyts was well tolerated in some situations but not in others both in vitro and in vivo. This was related to the cell type, the organ or the route of inoculation. Depending on the cell type, different cellular proteins, for example Hexim1 and Rbbp4, were found to be associated with oriLyt DNA...
March 2016: PLoS Pathogens
Gaspar J Kitange, Ann C Mladek, Mark A Schroeder, Jenny C Pokorny, Brett L Carlson, Yuji Zhang, Asha A Nair, Jeong-Heon Lee, Huihuang Yan, Paul A Decker, Zhiguo Zhang, Jann N Sarkaria
Here we provide evidence that RBBP4 modulates temozolomide (TMZ) sensitivity through coordinate regulation of two key DNA repair genes critical for recovery from TMZ-induced DNA damage: methylguanine-DNA-methyltransferase (MGMT) and RAD51. Disruption of RBBP4 enhanced TMZ sensitivity, induced synthetic lethality to PARP inhibition, and increased DNA damage signaling in response to TMZ. Moreover, RBBP4 silencing enhanced TMZ-induced H2AX phosphorylation and apoptosis in GBM cells. Intriguingly, RBBP4 knockdown suppressed the expression of MGMT, RAD51, and other genes in association with decreased promoter H3K9 acetylation (H3K9Ac) and increased H3K9 tri-methylation (H3K9me3)...
March 22, 2016: Cell Reports
Paulo R Adona, Cláudia L V Leal, Fernando H Biase, Tiago H De Bem, Lígia G Mesquita, Flávio V Meirelles, André L Ferraz, Luiz R Furlan, Paulo S Monzani, Samuel Guemra
Gene expression profiling of in vivo- and in vitro-matured bovine oocytes can identify transcripts related to the developmental potential of oocytes. Nonetheless, the effects of in vitro culturing oocytes are yet to be fully understood. We tested the effects of in vitro maturation on the transcript profile of oocytes collected from Bos taurus indicus cows. We quantified the expression of 1488 genes in in vivo- and in vitro-matured oocytes. Of these, 51 genes were up-regulated, whereas 56 were down-regulated (≥2-fold) in in vivo-matured oocytes in comparison with in vitro-matured oocytes...
August 2016: Zygote: the Biology of Gametes and Early Embryos
Akira Tsujii, Yoichi Miyamoto, Tetsuji Moriyama, Yuko Tsuchiya, Chikashi Obuse, Kenji Mizuguchi, Masahiro Oka, Yoshihiro Yoneda
Nucleocytoplasmic trafficking is a fundamental cellular process in eukaryotic cells. Here, we demonstrated that retinoblastoma-binding protein 4 (RBBP4) functions as a novel regulatory factor to increase the efficiency of importin α/β-mediated nuclear import. RBBP4 accelerates the release of importin β1 from importin α via competitive binding to the importin β-binding domain of importin α in the presence of RanGTP. Therefore, it facilitates importin α/β-mediated nuclear import. We showed that the importin α/β pathway is down-regulated in replicative senescent cells, concomitant with a decrease in RBBP4 level...
December 4, 2015: Journal of Biological Chemistry
Wei Wang, Yongju Lu, Paul M Stemmer, Xiangmin Zhang, Yongyi Bi, Zhengping Yi, Fei Chen
To investigate how mineral dust-induced gene (mdig, also named as mina53, MINA, or NO52) promotes carcinogenesis through inducing active chromatin, we performed proteomics analyses for the interacting proteins that were co-immunoprecipitated by anti-mdig antibody from either the lung cancer cell line A549 cells or the human bronchial epithelial cell line BEAS-2B cells. On SDS-PAGE gels, three to five unique protein bands were consistently observed in the complexes pulled-down by mdig antibody, but not the control IgG...
September 29, 2015: Oncotarget
Georgios D Vavougios, Evgeniy I Solenov, Chrissi Hatzoglou, Galina S Baturina, Liubov E Katkova, Paschalis Adam Molyvdas, Konstantinos I Gourgoulianis, Sotirios G Zarogiannis
The aim of our study was to assess the differential gene expression of Parkinson protein 7 (PARK7) interactome in malignant pleural mesothelioma (MPM) using data mining techniques to identify novel candidate genes that may play a role in the pathogenicity of MPM. We constructed the PARK7 interactome using the ConsensusPathDB database. We then interrogated the Oncomine Cancer Microarray database using the Gordon Mesothelioma Study, for differential gene expression of the PARK7 interactome. In ConsensusPathDB, 38 protein interactors of PARK7 were identified...
October 1, 2015: American Journal of Physiology. Lung Cellular and Molecular Physiology
Hodaka Kitamura, Eiko Ozono, Ritsuko Iwanaga, Andrew P Bradford, Junko Okuno, Emi Shimizu, Kenta Kurayoshi, Kazuyuki Kugawa, Hiroyuki Toh, Kiyoshi Ohtani
The transcription factor E2F is the principal target of the tumor suppressor pRB. E2F plays crucial roles not only in cell proliferation by activating growth-related genes but also in tumor suppression by activating pro-apoptotic and growth-suppressive genes. We previously reported that, in human normal fibroblasts, the tumor suppressor genes ARF, p27(Kip1) and TAp73 are activated by deregulated E2F activity induced by forced inactivation of pRB, but not by physiological E2F activity induced by growth stimulation...
September 2015: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Jing Tang, Liang Li, Wentao Huang, Chengjun Sui, Yingcheng Yang, Ximeng Lin, Guojun Hou, Xin Chen, Jing Fu, Shengxian Yuan, Shao Li, Wen Wen, Shanhua Tang, Dan Cao, Mengchao Wu, Lei Chen, Hongyang Wang
Epigenetic modification of miR-429 can manipulate liver T-ICs via targeting the RBBP4/E2F1/Oct4 axis, which might be crucial for hepatocarcinogenesis. However, whether miR-429 plays a role in regulating metastasis of hepatocellular carcinoma is still unclear. Using quantitative methylation analysis and real-time PCR, we have identified the hypomethylated status and upregulation of miR-429 in portal vein metastasis samples in comparison with their matched primary tumor. The ectopic expression of miR-429 dramatically induced the expression of MMP2/7/9 and enhanced HCC migration and invasion in vitro and in vivo in an EMT-independent manner...
August 1, 2015: Cancer Letters
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
Ahmed Z Balboula, Paula Stein, Richard M Schultz, Karen Schindler
During meiosis I (MI) in oocytes, the maturation-associated decrease of histone acetylation is critical for normal meiotic progression and accurate chromosome segregation. RBBP4 is a component of several different histone deacetylase containing chromatin-remodeling complexes, but RBBP4's role in regulating MI is not known. Depleting RBBP4 in mouse oocytes resulted in multipolar spindles at metaphase (Met) I with subsequent perturbed meiotic progression and increased incidence of abnormal spindles, chromosome misalignment, and aneuploidy at Met II...
April 2015: Biology of Reproduction
Gregory J Berry, Christine Frielle, Thaiphi Luu, Anna C Salzberg, Daniel B Rainbow, Linda S Wicker, Hanspeter Waldner
Type 1 diabetes (T1D) is a polygenic disease with multiple insulin-dependent diabetes (Idd) loci predisposing humans and NOD mice to disease. NOD.B10 Idd9 congenic mice, in which the NOD Idd9 chromosomal region is replaced by the Idd9 from T1D-resistant C57BL/10 mice, are significantly protected from T1D development. However, the genes and pathways conferring T1D development or protection by Idd9 remain to be fully elucidated. We have developed novel NOD.B10-Idd9 (line 905) congenic mice that predominantly harbor islet-reactive CD4(+) T cells expressing the BDC2...
March 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Zhonghua Liu, Fudong Li, Beibei Zhang, Sai Li, Jihui Wu, Yunyu Shi
The NuRD complex is a conserved transcriptional coregulator that contains both chromatin-remodeling and histone deacetylase activities. Mutations of PHF6 are found in patients with Börjeson-Forssman-Lehmann syndrome, T-cell acute lymphoblastic leukemia, or acute myeloid leukemia. Recently, PHF6 was identified to interact with the NuRD complex, and this interaction is mediated by the RBBP4 component. However, little is known about the molecular basis for the interaction. Here, we present the crystal structure of the complex of the NuRD subunit RBBP4 bound to the PHF6 peptide (residues 162-170)...
March 6, 2015: Journal of Biological Chemistry
Angela V Krüger, Rob Jelier, Oleh Dzyubachyk, Timo Zimmerman, Erik Meijering, Ben Lehner
Chromatin regulators are widely expressed proteins with diverse roles in gene expression, nuclear organization, cell cycle regulation, pluripotency, physiology and development, and are frequently mutated in human diseases such as cancer. Their inhibition often results in pleiotropic effects that are difficult to study using conventional approaches. We have developed a semi-automated nuclear tracking algorithm to quantify the divisions, movements and positions of all nuclei during the early development of Caenorhabditis elegans and have used it to systematically study the effects of inhibiting chromatin regulators...
February 15, 2015: Developmental Biology
Susan L Kloet, H Irem Baymaz, Matthew Makowski, Vincent Groenewold, Pascal W T C Jansen, Madeleine Berendsen, Hassin Niazi, Geert J Kops, Michiel Vermeulen
UNLABELLED: The nucleosome remodeling and deacetylase (NuRD) complex is an evolutionarily conserved chromatin-associated protein complex. Although the subunit composition of the mammalian complex is fairly well characterized, less is known about the stability and dynamics of these interactions. Furthermore, detailed information regarding protein-protein interaction surfaces within the complex is still largely lacking. Here, we show that the NuRD complex interacts with a number of substoichiometric zinc finger-containing proteins...
May 2015: FEBS Journal
Catherine Pfefferli, Fritz Müller, Anna Jaźwińska, Chantal Wicky
BACKGROUND: Epimorphic regeneration of a missing appendage in fish and urodele amphibians involves the creation of a blastema, a heterogeneous pool of progenitor cells underneath the wound epidermis. Current evidence indicates that the blastema arises by dedifferentiation of stump tissues in the vicinity of the amputation. In response to tissue loss, silenced developmental programs are reactivated to form a near-perfect copy of the missing body part. However, the importance of chromatin regulation during epimorphic regeneration remains poorly understood...
2014: BMC Biology
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