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Three-Dimensional Genomic Structure and Cohesin Occupancy Correlate with Transcriptional Activity during Spermatogenesis.
Vara C, Paytuví-Gallart A, Cuartero Y, Le Dily F, Garcia F, Salvà-Castro J, Gómez-H L, Julià E, Moutinho C, Aiese Cigliano R, Sanseverino W, Fornas O, Pendás AM, Heyn H, Waters PD, Marti-Renom MA, Ruiz-Herrera A
Mammalian gametogenesis involves dramatic and tightly regulated chromatin remodeling, whose regulatory pathways remain largely unexplored. Here, we generate a comprehensive high-resolution structural and functional atlas of mouse spermatogenesis by combining in situ chromosome conformation capture sequencing (Hi-C),... |
Resveratrol up-regulates ATP2A3 gene expression in breast cancer cell lines through epigenetic mechanisms.
Izquierdo-Torres E, Hernández-Oliveras A, Meneses-Morales I, Rodríguez G, Fuentes-García G, Zarain-Herzberg Á
Resveratrol (RSV) is a phytoestrogen which has been related to chemoprevention of several types of cancer. In this work, we show up to a 6-fold increased expression of ATP2A3 gene induced by RSV that triggers apoptosis and changes of intracellular Ca management in MCF-7 and MDA-MB-231 breast cancer cell lines. We ex... |
Global distribution of DNA hydroxymethylation and DNA methylation in chronic lymphocytic leukemia.
Wernig-Zorc S, Yadav MP, Kopparapu PK, Bemark M, Kristjansdottir HL, Andersson PO, Kanduri C, Kanduri M
BACKGROUND: Chronic lymphocytic leukemia (CLL) has been a good model system to understand the functional role of 5-methylcytosine (5-mC) in cancer progression. More recently, an oxidized form of 5-mC, 5-hydroxymethylcytosine (5-hmC) has gained lot of attention as a regulatory epigenetic modification with prognostic ... |
Genomic Location of PRMT6-Dependent H3R2 Methylation Is Linked to the Transcriptional Outcome of Associated Genes.
Bouchard C, Sahu P, Meixner M, Nötzold RR, Rust MB, Kremmer E, Feederle R, Hart-Smith G, Finkernagel F, Bartkuhn M, Savai Pullamsetti S, Nist A, Stiewe T, Philipsen S, Bauer UM
Protein arginine methyltransferase 6 (PRMT6) catalyzes asymmetric dimethylation of histone H3 at arginine 2 (H3R2me2a). This mark has been reported to associate with silent genes. Here, we use a cell model of neural differentiation, which upon PRMT6 knockout exhibits proliferation and differentiation defects. S... |
High-fidelity CRISPR/Cas9- based gene-specific hydroxymethylation rescues gene expression and attenuates renal fibrosis.
Xingbo Xu, Xiaoying Tan, Björn Tampe, Tim Wilhelmi, Melanie S. Hulshoff, Shoji Saito, Tobias Moser, Raghu Kalluri, Gerd Hasenfuss, Elisabeth M. Zeisberg & Michael Zeisberg
While suppression of specific genes through aberrant promoter methylation contributes to different diseases including organ fibrosis, gene-specific reactivation technology is not yet available for therapy. TET enzymes catalyze hydroxymethylation of methylated DNA, reactivating gene expression. We here report generat... |
Human papillomavirus type 16 antagonizes IRF6 regulation of IL-1β.
Ainouze M, Rochefort P, Parroche P, Roblot G, Tout I, Briat F, Zannetti C, Marotel M, Goutagny N, Auron P, Traverse-Glehen A, Lunel-Potencier A, Golfier F, Masson M, Robitaille A, Tommasino M, Carreira C, Walzer T, Henry T, Zanier K, Trave G, Hasan UA
Human papillomavirus type 16 (HPV16) and other oncoviruses have been shown to block innate immune responses and to persist in the host. However, to avoid viral persistence, the immune response attempts to clear the infection. IL-1β is a powerful cytokine produced when viral motifs are sensed by innate receptors... |
Human papillomavirus type 16 antagonizes IRF6 regulation of IL-1β.
Ainouze M, Rochefort P, Parroche P, Roblot G, Tout I, Briat F, Zannetti C, Marotel M, Goutagny N, Auron P, Traverse-Glehen A, Lunel-Potencier A, Golfier F, Masson M, Robitaille A, Tommasino M, Carreira C, Walzer T, Henry T, Zanier K, Trave G, Hasan UA
Human papillomavirus type 16 (HPV16) and other oncoviruses have been shown to block innate immune responses and to persist in the host. However, to avoid viral persistence, the immune response attempts to clear the infection. IL-1β is a powerful cytokine produced when viral motifs are sensed by innate receptors... |
CTCF-KDM4A complex correlates with histone modifications that negatively regulate gene expression in cancer cell lines.
Guerra-Calderas L, González-Barrios R, Patiño CC, Alcaraz N, Salgado-Albarrán M, de León DC, Hernández CC, Sánchez-Pérez Y, Maldonado-Martínez HA, De la Rosa-Velazquez IA, Vargas-Romero F, Herrera LA, García-Carrancá A, Soto-Reyes E
Histone demethylase KDM4A is involved in H3K9me3 and H3K36me3 demethylation, which are epigenetic modifications associated with gene silencing and RNA Polymerase II elongation, respectively. is abnormally expressed in cancer, affecting the expression of multiple targets, such as the gene. This enzyme localizes at th... |
The CUE1 domain of the SNF2-like chromatin remodeler SMARCAD1 mediates its association with KRAB-associated protein 1 (KAP1) and KAP1 target genes.
Ding D, Bergmaier P, Sachs P, Klangwart M, Rückert T, Bartels N, Demmers J, Dekker M, Poot RA, Mermoud JE
Chromatin in embryonic stem cells (ESCs) differs markedly from that in somatic cells, with ESCs exhibiting a more open chromatin configuration. Accordingly, ATP-dependent chromatin remodeling complexes are important regulators of ESC homeostasis. Depletion of the remodeler SMARCAD1, an ATPase of the SNF2 family, has... |
Miz1 Controls Schwann Cell Proliferation via H3K36me2 Demethylase Kdm8 to Prevent Peripheral Nerve Demyelination
Fuhrmann D. et al.
Schwann cell differentiation and myelination depends on chromatin remodeling, histone acetylation, and methylation, which all affect Schwann cell proliferation. We previously reported that the deletion of the POZ (POxvirus and Zinc finger) domain of the transcription factor Miz1 (Myc-interacting zinc finger protein;... |
The CUE1 domain of the SNF2-like chromatin remodeler SMARCAD1 mediates its association with KRAB-associated protein 1 (KAP1) and KAP1 target genes
Dong Ding et. al.
Chromatin in embryonic stem cells (ESCs) differs markedly from that in somatic cells, with ESCs exhibiting a more open chromatin configuration. Accordingly, ATP-dependent chromatin remodeling complexes are important regulators of ESC homeostasis. Depletion of the remodeler SMARCAD1, an ATPase of the SNF2 family, has... |
Individual effects of the copia and gypsy enhancer and insulator on chromatin marks, eRNA synthesis, and binding of insulator proteins in transfected genetic constructs.
Fedoseeva D.M. et al.
Enhancers and insulators are involved in the regulation of gene expression, but the basic underlying mechanisms of action of these elements are unknown. We analyzed the individual effects of the enhancer and the insulator from Drosophila mobile elements copia [enh(copia)] and gypsy using transfected genetic construc... |
UV Radiation Activates Toll-Like Receptor 9 Expression in Primary Human Keratinocytes, an Event Inhibited by Human Papillomavirus 38 E6 and E7 Oncoproteins
Pacini L. et al.
Several lines of evidence indicate that cutaneous human papillomavirus (HPV) types belonging to the beta genus of the HPV phylogenetic tree synergize with UV radiation in the development of skin cancer. Accordingly, the E6 and E7 oncoproteins from some beta HPV types are able to deregulate pathways related to immune... |
The cardiac calsequestrin gene transcription is modulated at the promoter by NFAT and MEF-2 transcription factors
Rafael Estrada-Avilés, Gabriela Rodríguez, Angel Zarain-Herzberg
Calsequestrin-2 (CASQ2) is the main Ca2+-binding protein inside the sarcoplasmic reticulum of cardiomyocytes. Previously, we demonstrated that MEF-2 and SRF binding sites within the human CASQ2 gene (hCASQ2) promoter region are functional in neonatal cardiomyocytes. In this work, we investigated if the calcineurin/N... |
The cardiac calsequestrin gene transcription is modulated at the promoter by NFAT and MEF-2 transcription factors.
Estrada-Avilés R. et al.
Calsequestrin-2 (CASQ2) is the main Ca2+-binding protein inside the sarcoplasmic reticulum of cardiomyocytes. Previously, we demonstrated that MEF-2 and SRF binding sites within the human CASQ2 gene (hCASQ2) promoter region are functional in neonatal cardiomyocytes. In this work, we investigated if the calcineurin/N... |
Viral driven epigenetic events alter the expression of cancer-related genes in Epstein-Barr-virus naturally infected Burkitt lymphoma cell lines
Hernandez-Vargas H. et al.
Epstein-Barr virus (EBV) was identified as the first human virus to be associated with a human malignancy, Burkitt’s lymphoma (BL), a pediatric cancer endemic in sub-Saharan Africa. The exact mechanism of how EBV contributes to the process of lymphomagenesis is not fully understood. Recent studies have highlig... |
SOX2 as a New Regulator of HPV16 Transcription
Martínez-Ramírez I. et al.
Persistent infections with high-risk human papillomavirus (HPV) constitute the main risk factor for cervical cancer development. HPV16 is the most frequent type associated to squamous cell carcinomas (SCC), followed by HPV18. The long control region (LCR) in the HPV genome contains the replication origin and sequenc... |
Biphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes
Kobayashi H. et al.
In vitro studies have shown that Rela/p65, a key subunit mediating NF-κB signalling, is involved in chondrogenic differentiation, cell survival and catabolic enzyme production. Here, we analyse in vivo functions of Rela in embryonic limbs and adult articular cartilage, and find that Rela protects chondrocytes ... |
Esrrb directly binds to Gata6 promoter and regulates its expression with Dax1 and Ncoa3
Uranishi K et al.
Estrogen-related receptor beta (Esrrb) is expressed in embryonic stem (ES) cells and is involved in self-renewal ability and pluripotency. Previously, we found that Dax1 is associated with Esrrb and represses its transcriptional activity. Further, the disruption of the Dax1-Esrrb interaction increases the expression... |
Chromatin remodeling regulates catalase expression during cancer cells adaptation to chronic oxidative stress.
Glorieux C. et al.
Regulation of ROS metabolism plays a major role in cellular adaptation to oxidative stress in cancer cells, but the molecular mechanism that regulates catalase, a key antioxidant enzyme responsible for conversion of hydrogen peroxide to water and oxygen, remains to be elucidated. Therefore, we investigated the trans... |
Induction of cell differentiation activates transcription of the Sarco/Endoplasmic Reticulum calcium-ATPase 3 gene (ATP2A3) in gastric and colon cancer cells
Flores-Peredo L et al.
The Sarco/Endoplasmic Reticulum Ca2+ -ATPases (SERCAs), pump Ca2+ into the endoplasmic reticulum lumen modulating cytosolic Ca2+ concentrations to regulate various cellular processes including cell growth. Previous studies have reported a downregulation of SERCA3 protein expression in gastric and colon cancer cell l... |
Regulatory Interaction between the Cellular Restriction Factor IFI16 and Viral pp65 (pUL83) Modulates Viral Gene Expression and IFI16 Protein Stability
Biolatti M et al.
A key player in the intrinsic resistance against human cytomegalovirus (HCMV) is the interferon-γ-inducible protein 16 (IFI16), which behaves as a viral DNA sensor in the first hours post infection and as a repressor of viral gene transcription in the later stages. Previous studies on HCMV replication demonstr... |
miR-125b-1 is repressed by histone modifications in breast cancer cell lines
Cisneros-Soberanis F et al.
PURPOSE:
Downregulation of miR-125b-1 is associated with poor prognosis in breast cancer patients. In this work we investigated the effect of histone modifications on the regulation of this gene promoter.
METHODS AND RESULTS:
We evaluated the enrichment of two histone modifications involved in gene repression, ... |
Osterix and RUNX2 are Transcriptional Regulators of Sclerostin in Human Bone
Flor M. Pérez-Campo, Ana Santurtún, Carmen García-Ibarbia, María A. Pascual, Carmen Valero, Carlos Garcés, Carolina Sañudo, María T. Zarrabeitia, José A. Riancho
Sclerostin, encoded by the SOST gene, works as an inhibitor of the Wnt pathway and therefore is an important regulator of bone homeostasis. Due to its potent action as an inhibitor of bone formation, blocking sclerostin activity is the purpose of recently developed anti-osteoporotic treatments. Two bone-specific tra... |
DNMT1 and HDAC2 Cooperate to Facilitate Aberrant Promoter Methylation in Inorganic Phosphate-Induced Endothelial-Mesenchymal Transition
Tan X et al.
While phosphorus in the form of inorganic or organic phosphate is critically involved in most cellular functions, high plasma levels of inorganic phosphate levels have emerged as independent risk factor for cardiac fibrosis, cardiovascular morbidity and decreased life-expectancy. While the link of high phosphate and... |
