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Tatiana Souslova, Kim Mirédin, Anne M Millar, Paul R Albert
Five-prime repressor element under dual repression binding protein-1 (Freud-1)/CC2D1A is genetically linked to intellectual disability and implicated in neuronal development. Freud-1 represses the serotonin-1A (5-HT1A) receptor gene HTR1A by histone deacetylase (HDAC)-dependent or HDAC-independent mechanisms in 5-HT1A-negative (e.g., HEK-293) or 5-HT1A-expressing cells (SK-N-SH), respectively. To identify the underlying mechanisms, Freud-1-associated proteins were affinity-purified from HEK-293 nuclear extracts and members of the Brg1/SMARCCA chromatin remodeling and Sin3A-HDAC corepressor complexes were identified...
December 2, 2016: Molecular Neurobiology
Christina Bachmann, Huong Nguyen, Joachim Rosenbusch, Linh Pham, Tamara Rabe, Megha Patwa, Godwin Sokpor, Rho H Seong, Ruth Ashery-Padan, Ahmed Mansouri, Anastassia Stoykova, Jochen F Staiger, Tran Tuoc
Neurogenesis is a key developmental event through which neurons are generated from neural stem/progenitor cells. Chromatin remodeling BAF (mSWI/SNF) complexes have been reported to play essential roles in the neurogenesis of the central nervous system. However, whether BAF complexes are required for neuron generation in the olfactory system is unknown. Here, we identified onscBAF and ornBAF complexes, which are specifically present in olfactory neural stem cells (oNSCs) and olfactory receptor neurons (ORNs), respectively...
September 2016: PLoS Genetics
Lu Wang, Zibo Zhao, Mark B Meyer, Sandeep Saha, Menggang Yu, Ailan Guo, Kari B Wisinski, Wei Huang, Weibo Cai, J Wesley Pike, Ming Yuan, Paul Ahlquist, Wei Xu
No abstract text is available yet for this article.
July 11, 2016: Cancer Cell
Prasenjit Sarkar, Adam Mischler, Shan M Randall, Timothy S Collier, Karen F Dorman, Kim A Boggess, David C Muddiman, Balaji M Rao
Human embryonic stem cells (hESCs) have been used to derive trophoblasts through differentiation in vitro. Intriguingly, mouse ESCs are prevented from differentiation to trophoblasts by certain epigenetic factor proteins such as Dnmt1, thus necessitating the study of epigenetic factor proteins during hESC differentiation to trophoblasts. We used stable isotope labeling by amino acids in cell culture and quantitative proteomics to study changes in the nuclear proteome during hESC differentiation to trophoblasts and identified changes in the expression of 30 epigenetic factor proteins...
August 5, 2016: Journal of Proteome Research
Sneha Lal, Md Maksudul Alam, Jagmohan Hooda, Ajit Shah, Thai M Cao, Zhenyu Xuan, Li Zhang
Recent experimental evidence increasingly shows that the dysregulation of cellular bioenergetics is associated with a wide array of common human diseases, including cancer, neurological diseases and diabetes. Respiration provides a vital source of cellular energy for most eukaryotic cells, particularly high energy demanding cells. However, the understanding of how respiration is globally regulated is very limited. Interestingly, recent evidence suggests that Swi3 is an important regulator of respiration genes in yeast...
July 2016: Bioscience Reports
Huong Nguyen, Godwin Sokpor, Linh Pham, Joachim Rosenbusch, Anastassia Stoykova, Jochen F Staiger, Tran Tuoc
The multi-subunit chromatin-remodeling SWI/SNF (known as BAF for Brg/Brm-associated factor) complexes play essential roles in development. Studies have shown that the loss of individual BAF subunits often affects local chromatin structure and specific transcriptional programs. However, we do not fully understand how BAF complexes function in development because no animal mutant had been engineered to lack entire multi-subunit BAF complexes. Importantly, we recently reported that double conditional knock-out (dcKO) of the BAF155 and BAF170 core subunits in mice abolished the presence of the other BAF subunits in the developing cortex...
May 18, 2016: Cell Cycle
Maryna Panamarova, Andy Cox, Krzysztof B Wicher, Richard Butler, Natalia Bulgakova, Shin Jeon, Barry Rosen, Rho H Seong, William Skarnes, Gerald Crabtree, Magdalena Zernicka-Goetz
Dynamic control of gene expression is essential for the development of a totipotent zygote into an embryo with defined cell lineages. The accessibility of genes responsible for cell specification to transcriptional machinery is dependent on chromatin remodelling complexes such as the SWI\SNF (BAF) complex. However, the role of the BAF complex in early mouse development has remained unclear. Here, we demonstrate that BAF155, a major BAF complex subunit, regulates the assembly of the BAF complex in vivo and regulates lineage specification of the mouse blastocyst...
April 15, 2016: Development
Ramanathan Narayanan, Mehdi Pirouz, Cemil Kerimoglu, Linh Pham, Robin J Wagener, Kamila A Kiszka, Joachim Rosenbusch, Rho H Seong, Michael Kessel, Andre Fischer, Anastassia Stoykova, Jochen F Staiger, Tran Tuoc
BAF (Brg/Brm-associated factors) complexes play important roles in development and are linked to chromatin plasticity at selected genomic loci. Nevertheless, a full understanding of their role in development and chromatin remodeling has been hindered by the absence of mutants completely lacking BAF complexes. Here, we report that the loss of BAF155/BAF170 in double-conditional knockout (dcKO) mice eliminates all known BAF subunits, resulting in an overall reduction in active chromatin marks (H3K9Ac), a global increase in repressive marks (H3K27me2/3), and downregulation of gene expression...
December 1, 2015: Cell Reports
Timothy S Carey, Zubing Cao, Inchul Choi, Avishek Ganguly, Catherine A Wilson, Soumen Paul, Jason G Knott
During mouse preimplantation development, the generation of the inner cell mass (ICM) and trophoblast lineages comprises upregulation of Nanog expression in the ICM and its silencing in the trophoblast. However, the underlying epigenetic mechanisms that differentially regulate Nanog in the first cell lineages are poorly understood. Here, we report that BRG1 (Brahma-related gene 1) cooperates with histone deacetylase 1 (HDAC1) to regulate Nanog expression. BRG1 depletion in preimplantation embryos and Cdx2-inducible embryonic stem cells (ESCs) revealed that BRG1 is necessary for Nanog silencing in the trophoblast lineage...
December 2015: Molecular and Cellular Biology
Serena Muratcioglu, Diego M Presman, John R Pooley, Lars Grøntved, Gordon L Hager, Ruth Nussinov, Ozlem Keskin, Attila Gursoy
The glucocorticoid receptor (GR) is a steroid-hormone-activated transcription factor that modulates gene expression. Transcriptional regulation by the GR requires dynamic receptor binding to specific target sites located across the genome. This binding remodels the chromatin structure to allow interaction with other transcription factors. Thus, chromatin remodeling is an essential component of GR-mediated transcriptional regulation, and understanding the interactions between these molecules at the structural level provides insights into the mechanisms of how GR and chromatin remodeling cooperate to regulate gene expression...
September 15, 2015: Biophysical Journal
H-J Li, P-N Yu, K-Y Huang, H-Y Su, T-H Hsiao, C-P Chang, M-H Yu, Y-W Lin
The transcription factor NKX6.1 (NK6 homeobox 1) is important in the development of pancreatic β-cells and neurons. Although recent publications show that NKX6.1 is hypermethylated and downregulated during tumorigenesis, the function of NKX6.1 in carcinogenesis remains elusive. Here, we address the metastasis suppressor function of human NKX6.1 using cell, animal and clinical analyses. Our data show that NKX6.1 represses tumor formation and metastatic ability both in vitro and in vivo. Mechanistically, NKX6...
April 28, 2016: Oncogene
Zongliang Jiang, Yong Tang, Xueming Zhao, Mingyuan Zhang, David M Donovan, Xiuchun Cindy Tian
The SWI/SNF (SWItch/Sucrose NonFermentable or BAF, Brg/Brahma-associated factors) complexes are epigenetic modifiers of chromatin structure and undergo progressive changes in subunit composition during cellular differentiation. For example, in embryonic stem cells, esBAF contains Brg1 and Baf155, while their homologs, Brm and Baf170, are present in BAF of somatic cells. In this study, we sought to determine whether Brm and Baf170 play any roles in induced pluripotent stem cell (iPSC) reprogramming by using shRNA-mediated knockdown studies in the mouse model...
October 1, 2015: Stem Cells and Development
Olafur A Stefansson, Manel Esteller
In a recent article, Wang and colleagues reported the discovery of a mechanism by which CARM1 regulates the genomic localization of BAF155 (a SWI/SNF subunit involved in chromatin remodeling) through post-translational methylation at R1064 arginine residues. This modification leads to the relocalization of BAF155-containing SWI/SNF complexes to regions containing genes involved in the Myc oncogenic pathway. The results presented are evidence that these interactions constitute a mechanism by which the BAF155 chromatin remodeling factor contributes to cancer...
May 19, 2014: Breast Cancer Research: BCR
Xiaoli Zhang, Bing Li, Wenguo Li, Lijuan Ma, Dongyan Zheng, Leping Li, Weijing Yang, Min Chu, Wei Chen, Richard B Mailman, Jun Zhu, Guoping Fan, Trevor K Archer, Yuan Wang
The SWI/SNF complex plays an important role in mouse embryonic stem cells (mESCs), but it remains to be determined whether this complex is required for the pluripotency of human ESCs (hESCs). Using RNAi, we demonstrated that depletion of BRG1, the catalytic subunit of the SWI/SNF complex, led to impaired self-renewing ability and dysregulated lineage specification of hESCs. A unique composition of the BRG1-SWI/SNF complex in hESCs was further defined by the presence of BRG1, BAF250A, BAF170, BAF155, BAF53A, and BAF47...
September 9, 2014: Stem Cell Reports
Li Li, Xiang-Shan Fan, Qiu-Yuan Xia, Qiu Rao, Biao Liu, Bo Yu, Qun-Li Shi, Zhen-Feng Lu, Xiao-Jun Zhou
The loss of INI1 (SMARCB1) expression, caused by SMARCB1 (INI1, SNF5L4, BAF47) inactivation, frequently occurs in epithelioid sarcoma (ES) and could aid in confirming the diagnosis. Except for INI1, the expression of switch in mating type/sucrose nonfermentation complex members in ES has never been examined. In this study, the expression of key subunits of this complex-INI1, BRG1 (SMARCA4), BRM (SNF2L2, SMARCA2), PBRM1 (hPB1, BAF180), and BAF155 (SMARCC1)-was analyzed in 23 ES cases: 15 conventional and 8 proximal type...
November 2014: Human Pathology
Reiko Watanabe, Ayako Ui, Shin-Ichiro Kanno, Hideaki Ogiwara, Takahiro Nagase, Takashi Kohno, Akira Yasui
The SWI/SNF chromatin-remodeling family contains various protein complexes, which regulate gene expression during cellular development and influence DNA damage response in an ATP- and complex-dependent manner, of which details remain elusive. Recent human genome sequencing of various cancer cells revealed frequent mutations in SWI/SNF factors, especially ARID1A, a variant subunit in the BRG1-associated factor (BAF) complex of the SWI/SNF family. We combined live-cell analysis and gene-suppression experiments to show that suppression of either ARID1A or its paralog ARID1B led to reduced nonhomologous end joining activity of DNA double-strand breaks (DSB), decreased accumulation of KU70/KU80 proteins at DSB, and sensitivity to ionizing radiation, as well as to cisplatin and UV...
May 1, 2014: Cancer Research
Lu Wang, Zibo Zhao, Mark B Meyer, Sandeep Saha, Menggang Yu, Ailan Guo, Kari B Wisinski, Wei Huang, Weibo Cai, J Wesley Pike, Ming Yuan, Paul Ahlquist, Wei Xu
Coactivator-associated arginine methyltransferase 1 (CARM1), a coactivator for various cancer-relevant transcription factors, is overexpressed in breast cancer. To elucidate the functions of CARM1 in tumorigenesis, we knocked out CARM1 from several breast cancer cell lines using Zinc-Finger Nuclease technology, which resulted in drastic phenotypic and biochemical changes. The CARM1 KO cell lines enabled identification of CARM1 substrates, notably the SWI/SNF core subunit BAF155. Methylation of BAF155 at R1064 was found to be an independent prognostic biomarker for cancer recurrence and to regulate breast cancer cell migration and metastasis...
January 13, 2014: Cancer Cell
Xiaofeng Wang, Charles W M Roberts
In this issue of Cancer Cell, Wang and colleagues report that CARM1, a protein arginine methyltransferase, specifically methylates BAF155/SMARCC1, a core subunit of the SWI/SNF chromatin remodeling/tumor suppressor complex. This modification facilitates the targeting of BAF155 to genes of the c-Myc pathway and enhances breast cancer progression and metastasis.
January 13, 2014: Cancer Cell
Laura Harmacek, Dawn E Watkins-Chow, Jianfu Chen, Kenneth L Jones, William J Pavan, J Michael Salbaum, Lee Niswander
Failure of embryonic neural tube closure results in the second most common class of birth defects known as neural tube defects (NTDs). While NTDs are likely the result of complex multigenic dysfunction, it is not known whether polymorphisms in epigenetic regulators may be risk factors for NTDs. Here we characterized Baf155(msp3) , a unique ENU-induced allele in mice. Homozygous Baf155(mps3) embryos exhibit highly penetrant exencephaly, allowing us to investigate the roles of an assembled, but malfunctional BAF chromatin remodeling complex in vivo at the time of neural tube closure...
May 2014: Developmental Neurobiology
B Giessrigl, W M Schmidt, M Kalipciyan, M Jeitler, M Bilban, M Gollinger, S Krieger, W Jäger, R M Mader, G Krupitza
BACKGROUND: Breast cancer is the leading cause of cancer death in women living in the western hemisphere. Despite major advances in first-line endocrine therapy of advanced oestrogen receptor (ER)-positive breast cancer, the frequent recurrence of resistant cancer cells represents a serious obstacle to successful treatment. Understanding the mechanisms leading to acquired resistance, therefore, could pave the way to the development of second-line therapeutics. To this end, we generated an ER-positive breast cancer cell line (MCF-7) with resistance to the therapeutic anti-oestrogen fulvestrant (FUL) and studied the molecular changes involved in resistance...
November 12, 2013: British Journal of Cancer
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