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Miguel Vidal - One of the best experts on this subject based on the ideXlab platform.
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The chromatin nuclear protein NUPR1L is intrinsically disordered and binds to the same proteins as its paralogue
Biochemical Journal, 2018Co-Authors: Jose L. Neira, Miguel Vidal, Bruno Rizzuti, Maria Belen Lopez, Paz Sevilla, Ana Camara-artigas, Juan IovannaAbstract:NUPR1 is a protumoral multifunctional intrinsically disordered protein (IDP), which is activated during the acute phases of pancreatitis. It interacts with other IDPs such as prothymosin alpha, as well as with folded proteins such as the C-terminal region of RING1-B (C-RING1B) of the Polycomb complex; in all those interactions, residues around Ala33 and Thr68 (the `hot-spot' region) of NUPR1 intervene. Its paralogue, NUPR1L, is also expressed in response to DNA damage, it is p53-regulated, and its expression down-regulates that of the NUPR1 gene. In this work, we characterized the conformational preferences of isolated NUPR1L and its possible interactions with the same molecular partners of NUPR1. Our results show that NUPR1L was an oligomeric IDP from pH 2.0 to 12.0, as judged by steady-state fluorescence, circular dichroism (CD), dynamic light scattering, 1D H-1-NMR (nuclear magnetic resonance), and as indicated by structural modelling. However, in contrast with NUPR1, there was evidence of local helical- or turn-like structures; these structures were not rigid, as judged by the lack of sigmoidal behaviour in the chemical and thermal denaturation curves obtained by CD and fluorescence. Interestingly enough, NUPR1L interacted with prothymosin alpha and C-RING1B, and with a similar affinity to that of NUPR1 (in the low micromolar range). Moreover, NUPR1L hetero-associated with NUPR1 with an affinity of 0.4 mu M and interacted with the `hot-spot' region of NUPR1. Thus, we suggest that the regulation of NUPR1 gene by NUPR1L does not only happen at the DNA level, but It could also Involve direct interactions with NUPR1 natural partners.
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Intrinsically disordered chromatin protein NUPR1 binds to the C-terminal region of Polycomb RING1B
Proceedings of the National Academy of Sciences of the United States of America, 2017Co-Authors: Patricia Santofimia-castaño, Miguel Vidal, Bruno Rizzuti, Ángel Pey, Philippe Soubeyran, Raúl Urrutia, Juan Iovanna, José NeiraAbstract:Intrinsically disordered proteins (IDPs) are ubiquitous in eukaryotes, and they are often associated with diseases in humans. The protein NUPR1 is a multifunctional IDP involved in chromatin remodeling and in the development and progression of pancreatic cancer; however, the details of such functions are unknown. Polycomb proteins are involved in specific transcriptional cascades and gene silencing. One of the proteins of the Polycomb complex is the Ring finger protein 1 (RING1). RING1 is related to aggressive tumor features in multiple cancer types. In this work we characterized the interaction between NUPR1 and the paralogue RING1B in vitro, in silico, and in cellulo. The interaction occurred through the C-terminal region of RING1B (C-RING1B), with an affinity in the low micromolar range (∼10 μM). The binding region of NUPR1, mapped by NMR, was a hydrophobic polypeptide patch at the 30s region of its sequence, as pinpointed by computational results and site-directed mutagenesis at Ala33. The association between C-RING1B and wild-type NUPR1 also occurred in cellulo as tested by protein liga-tion assays; this interaction is inhibited by trifluoperazine, a drug known to hamper binding of wild-type NUPR1 with other proteins. Furthermore, the Thr68Gln and Ala33Gln/Thr68Gln mutants had a reduction in the binding toward C-RING1B as shown by in vitro, in silico, and in cellulo studies. This is an example of a well-folded partner of NUPR1, because its other interacting proteins are also unfolded. We hypothesize that NUPR1 plays an active role in chromatin remodeling and carcinogenesis, together with Polycomb proteins.
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RING1 proteins contribute to early proximal-distal specification of the forelimb bud by restricting Meis2 expression.
Development (Cambridge England), 2015Co-Authors: Nayuta Yakushiji-kaminatsui, Miguel Vidal, Takashi Kondo, Takaho A. Endo, Yoko Koseki, Kaori Kondo, Osamu Ohara, Haruhiko KosekiAbstract:Polycomb group (PcG) proteins play a pivotal role in silencing developmental genes and help to maintain various stem and precursor cells and regulate their differentiation. PcG factors also regulate dynamic and complex regional specification, particularly in mammals, but this activity is mechanistically not well understood. In this study, we focused on proximal-distal (PD) patterning of the mouse forelimb bud to elucidate how PcG factors contribute to a regional specification process that depends on developmental signals. Depletion of the RING1 proteins RING1A (RING1) and RING1B (RNF2), which are essential components of Polycomb repressive complex 1 (PRC1), led to severe defects in forelimb formation along the PD axis. We show that preferential defects in early distal specification in RING1A/B-deficient forelimb buds accompany failures in the repression of proximal signal circuitry bound by RING1B, including Meis1/2, and the activation of distal signal circuitry in the prospective distal region. Additional deletion of Meis2 induced partial restoration of the distal gene expression and limb formation seen in the RING1A/B-deficient mice, suggesting a crucial role for RING1-dependent repression of Meis2 and likely also Meis1 for distal specification. We suggest that the RING1-MEIS1/2 axis is regulated by early PD signals and contributes to the initiation or maintenance of the distal signal circuitry.
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polycomb potentiates meis2 activation in midbrain by mediating interaction of the promoter with a tissue specific enhancer
Developmental Cell, 2014Co-Authors: Takashi Kondo, Miguel Vidal, Takaho A. Endo, Kaori Kondo, Kyoichi Isono, Shigeyoshi Itohara, Haruhiko KosekiAbstract:Summary Polycomb -group ( Pc G) proteins mediate repression of developmental regulators in a reversible manner, contributing to their spatiotemporally regulated expression. However, it is poorly understood how Pc G-repressed genes are activated by developmental cues. Here, we used the mouse Meis2 gene as a model to identify a role of a tissue-specific enhancer in removing Pc G from the promoter. Meis2 repression in early development depends on binding of RING1B, an essential E3 component of Pc G, to its promoter, coupled with its association with another RING1B-binding site (RBS) at the 3′ end of the Meis2 gene. During early midbrain development, a midbrain-specific enhancer (MBE) transiently associates with the promoter-RBS, forming a promoter-MBE-RBS tripartite interaction in a RING1-dependent manner. Subsequently, RING1B-bound RBS dissociates from the tripartite complex, leaving promoter-MBE engagement to activate Meis2 expression. This study therefore demonstrates that Pc G and/or related factors play a role in Meis2 activation by regulating the topological transition of cis -regulatory elements.
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rybp represses endogenous retroviruses and preimplantation and germ line specific genes in mouse embryonic stem cells
Molecular and Cellular Biology, 2012Co-Authors: Kaori Hisada, Haruhiko Koseki, Takaho A. Endo, Carmen Sanchez, Mitsuhiro Endoh, Monica Romantrufero, Jafar Sharif, Miguel VidalAbstract:Polycomb repressive complexes (PRCs) are important chromatin regulators of embryonic stem (ES) cell function. RYBP binds Polycomb H2A monoubiquitin ligases RING1A and RING1B and has been suggested to assist PRC localization to their targets. Moreover, constitutive inactivation of RYBP precludes ES cell formation. Using ES cells conditionally deficient in RYBP, we found that RYBP is not required for maintenance of the ES cell state, although mutant cells differentiate abnormally. Genome-wide chromatin association studies showed RYBP binding to promoters of Polycomb targets, although its presence is dispensable for gene repression. We discovered, using Eed-knockout (KO) ES cells, that RYBP binding to promoters was independent of H3K27me3. However, recruiting of PRC1 subunits RING1B and Mel18 to their targets was not altered in the absence of RYBP. In contrast, we have found that RYBP efficiently represses endogenous retroviruses (murine endogenous retrovirus [MuERV] class) and preimplantation (including zygotic genome activation stage)- and germ line-specific genes. These observations support a selective repressor activity for RYBP that is dispensable for Polycomb function in the ES cell state. Also, they suggest a role for RYBP in epigenetic resetting during preimplantation development through repression of germ line genes and PcG targets before formation of pluripotent epiblast cells.
Arie P Otte - One of the best experts on this subject based on the ideXlab platform.
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polycomb group oncogenes ezh2 bmi1 and RING1 are overexpressed in prostate cancer with adverse pathologic and clinical features
European Urology, 2007Co-Authors: Geert J L H Van Leenders, Arie P Otte, D F Dukers, Daphne Hessels, Susan W M Van Den Kieboom, Christina A Hulsbergen, Alfred J Witjes, Chris J L M Meijer, Frank M RaaphorstAbstract:Abstract Objectives Polycomb group (PcG) proteins are involved in maintenance of cell identity and proliferation. The protein EZH2 is overexpressed in disseminated prostate cancer, implicating a role of PcG complexes in tumor progression. In this study, we evaluated the expression of eight members of both PcG complexes in clinicopathologically defined prostate cancer. Methods Components of both PcG protein complexes PRC2 (EZH2, EED, YY1) and PRC1 (BMI1, RING1, HPH1, HPC1, HPC2) were immunohistochemically identified in tissue microarrays of 114 prostate cancer patients. Protein expression was semi-quantitatively scored and correlated with pathologic parameters and recurrence of prostate-specific antigen (PSA). Results Whereas BMI1, RING1, HPC1 and HPH1 were all abundantly present in normal and malignant prostate epithelium, expression of EZH2 occurred in only Conclusions PcG proteins EZH2, BMI1, and RING1 are associated with adverse pathologic features and clinical PSA recurrence of prostate cancer. Whereas BMI1 and RING1 are abundantly present in prostate cancer, EZH2 is expressed at relatively low levels, making it a less obvious target for therapy.
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polycomb group proteins RING1a b link ubiquitylation of histone h2a to heritable gene silencing and x inactivation
Developmental Cell, 2004Co-Authors: Mariana De Napoles, Arie P Otte, Jacqueline E Mermoud, Rika Wakao, Amy Y Tang, Mitusuhiro Endoh, Ruth Appanah, Tatyana B Nesterova, Jose C R Silva, Miguel VidalAbstract:Abstract In many higher organisms, 5%–15% of histone H2A is ubiquitylated at lysine 119 (uH2A). The function of this modification and the factors involved in its establishment, however, are unknown. Here we demonstrate that uH2A occurs on the inactive X chromosome in female mammals and that this correlates with recruitment of Polycomb group (PcG) proteins belonging to Polycomb repressor complex 1 (PRC1). Based on our observations, we tested the role of the PRC1 protein RING1B and its closely related homolog RING1A in H2A ubiquitylation. Analysis of RING1B null embryonic stem (ES) cells revealed extensive depletion of global uH2A levels. On the inactive X chromosome, uH2A was maintained in RING1A or RING1B null cells, but not in double knockout cells, demonstrating an overlapping function for these proteins in development. These observations link H2A ubiquitylation, X inactivation, and PRC1 PcG function, suggesting an unanticipated and novel mechanism for chromatin-mediated heritable gene silencing.
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RING1 interacts with multiple polycomb group proteins and displays tumorigenic activity
Molecular and Cellular Biology, 1999Co-Authors: David P E Satijn, Arie P OtteAbstract:Polycomb-group (PcG) proteins form large multimeric protein complexes that are involved in maintaining the transcriptionally repressive state of genes. Previously, we reported that RING1 interacts with vertebrate Polycomb (Pc) homologs and is associated with or is part of a human PcG complex. However, very little is known about the role of RING1 as a component of the PcG complex. Here we undertake a detailed characterization of RING1 protein-protein interactions. By using directed two-hybrid and in vitro protein-protein analyses, we demonstrate that RING1, besides interacting with the human Pc homolog HPC2, can also interact with itself and with the vertebrate PcG protein BMI1. Distinct domains in the RING1 protein are involved in the self-association and in the interaction with BMI1. Further, we find that the BMI1 protein can also interact with itself. To better understand the role of RING1 in regulating gene expression, we overexpressed the protein in mammalian cells and analyzed differences in gene expression levels. This analysis shows that overexpression of RING1 strongly represses En-2, a mammalian homolog of the well-characterized Drosophila PcG target gene engrailed. Furthermore, RING1 overexpression results in enhanced expression of the proto-oncogenes c-jun and c-fos. The changes in expression levels of these proto-oncogenes are accompanied by cellular transformation, as judged by anchorage-independent growth and the induction of tumors in athymic mice. Our data demonstrate that RING1 interacts with multiple human PcG proteins, indicating an important role for RING1 in the PcG complex. Further, deregulation of RING1 expression leads to oncogenic transformation by deregulation of the expression levels of certain oncogenes.
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RING1a is a transcriptional repressor that interacts with the polycomb m33 protein and is expressed at rhombomere boundaries in the mouse hindbrain
The EMBO Journal, 1997Co-Authors: Jon Schoorlemmer, Arie P Otte, Emiliano Garcia, Camelia V Marcosgutierrez, Felipe Were, Rodrigo Andres Martinez, David P E Satijn, Miguel VidalAbstract:In Drosophila, the products of the Polycomb group (Pc-G) of genes act as chromatin-associated multimeric protein complexes that repress expression of homeotic genes. Vertebrate Pc-G homologues have been identified, but the nature of the complexes they form and the mechanisms of their action are largely unknown. The Polycomb homologue M33 is implicated in mesoderm patterning in the mouse and here we show that it acts as a transcriptional repressor in transiently transfected cells. Furthermore, we have identified two murine proteins, RING1A and RING1B, that interact directly with the repressor domain of M33. RING1A and RING1B display blocks of similarity throughout their sequences, including an N-terminal RING finger domain. However, the interaction with M33 occurs through a region at the C-terminus. RING1A represses transcription through sequences not involved in M33 binding. RING1A protein co-localizes in nuclear domains with M33 and other Pc-G homologues, such as Bmi1. The expression of RING1A at early stages of development is restricted to the neural tube, whereas M33 is expressed ubiquitously. Within the neural tube, RING1A RNA is located at the rhombomere boundaries of the hindbrain. Taken together, these data suggest that RING1A may contribute to a tissue-specific function of Pc-G-protein complexes during mammalian development.
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RING1 is associated with the polycomb group protein complex and acts as a transcriptional repressor
Molecular and Cellular Biology, 1997Co-Authors: David P E Satijn, M J Gunster, J Van Der Vlag, Karien M Hamer, Wouter Schul, Mark J Alkema, A J Saurin, Paul S Freemont, R Van Driel, Arie P OtteAbstract:The Polycomb (Pc) protein is a component of a multimeric, chromatin-associated Polycomb group (PcG) protein complex, which is involved in stable repression of gene activity. The identities of components of the PcG protein complex are largely unknown. In a two-hybrid screen with a vertebrate Pc homolog as a target, we identify the human RING1 protein as interacting with Pc. RING1 is a protein that contains the RING finger motif, a specific zinc-binding domain, which is found in many regulatory proteins. So far, the function of the RING1 protein has remained enigmatic. Here, we show that RING1 coimmunoprecipitates with a human Pc homolog, the vertebrate PcG protein BMI1, and HPH1, a human homolog of the PcG protein Polyhomeotic (Ph). Also, RING1 colocalizes with these vertebrate PcG proteins in nuclear domains of SW480 human colorectal adenocarcinoma and Saos-2 human osteosarcoma cells. Finally, we show that RING1, like Pc, is able to repress gene activity when targeted to a reporter gene. Our findings indicate that RING1 is associated with the human PcG protein complex and that RING1, like PcG proteins, can act as a transcriptional repressor.
John Trowsdale - One of the best experts on this subject based on the ideXlab platform.
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physical mapping 220 kb centromeric of the human mhc and dna sequence analysis of the 43 kb segment including the RING1 hke6 and hke4 genes
Genomics, 1997Co-Authors: Yara Yukie Kikuti, John Trowsdale, Gen Tamiya, Asako Ando, Lei Chen, Minoru Kimura, Euripides Ferreira, Kimiyoshi Tsuji, Hidetoshi InokoAbstract:Abstract A cosmid contig was constructed from a YAC clone with a 220-kb insert that spans the centromeric side of the human MHC class II region, corresponding to the mouse t complex. The gene order was identified to be HSET–HKE1.5–HKE2–HKE3–RING1–HKE6–HKE 4 (RING5). The genomic sequence of a 42,801-bp long region encoded by one cosmid clone in the RING1, HKE6, and HKE4 subregions was determined by the shotgun method. The exon–intron organization of these three genes, RING1 (Ring finger protein), HKE6 (steroid dehydrogenase-like protein), and HKE4 (transmembrane protein with histidine-rich charge clusters), was determined. The previously reported RING2 gene was revealed to be identical to HKE6. Transcripts from HKE4 were detected in the placenta, lung, kidney, and pancreas. Those of HKE6 were found in the liver and pancreas. The 25-kb region proximal to the RING1 gene includes an extensive dense cluster of Alu repeats (about 1.2 Alu per kb), and no gene has been identified in this so far. The region is equivalent to part of the mouse t complex and could be of relevance to human development.
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polymorphism in a second abc transporter gene located within the class ii region of the human major histocompatibility complex
Proceedings of the National Academy of Sciences of the United States of America, 1992Co-Authors: Stephen H Powis, Adrian Kelly, Richard Glynne, Stephan Beck, Ian Mockridge, Lesleyanne Kerr, Uzi Gileadi, John TrowsdaleAbstract:Abstract Recent studies have identified genes within the major histocompatibility complex (MHC) that may play a role in presentation of antigenic peptides to T cells. We have previously described RING4, a gene within the human MHC class II region that has sequence homology with members of the ABC ("ATP-binding cassette") transporter superfamily. We now report the nucleotide sequence of RING11, a second ABC transporter gene located approximately 7 kilobases telomeric to RING4, RING11 is gamma-interferon inducible, a property shared with other genes involved in antigen presentation. Comparison between the amino acid sequences of RING11 and RING4 reveals strong homology. We propose that they form a heterodimer that transports peptides from the cytoplasm into the endoplasmic reticulum. We have identified two RING11 alleles, which differ in the length of their derived protein sequence by 17 amino acids. The more common of these alleles is present in a Caucasoid population at a frequency of 79%.
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assembly and function of the two abc transporter proteins encoded in the human major histocompatibility complex
Nature, 1992Co-Authors: Adrian Kelly, Stephen H Powis, John Trowsdale, Ian Mockridge, Lesleyanne Kerr, Tim Elliott, Judy Bastin, Barbara Uchanskaziegler, Andreas Ziegler, Alain TownsendAbstract:PRESENTATION of cytoplasmic antigens to class I-restricted cytotoxic T cells implied the existence of a specialized peptide transporter1–3 (reviewed in ref. 4). For most class I heavy chains, association with peptides of the appropriate length is required for stable assembly with β 2-microglobulin5–11. Mutant cells RMA–S (ref. 12) and .174/T2 (refs 13,14) neither assemble stable class I molecules nor present intracellular antigens, and we have suggested that they have lost a function required for the transport of short peptides from the cytosol to the endoplasmic reticulum5–7. The genetic defect in .174 has been localized to a large deletion in the class II region of the major histocompatibility complex6,15,16, within which two genes (RING4 and RING11) have been identified that code for 'ABC' (ATP-binding cassette) transporters15,17–21. We report here that the protein products of these two genes assemble to form a complex. Defects in either protein result in the formation of unstable class I molecules and loss of presentation of intracellular antigens. The molecular defect in a new mutant, BM36.1, is shown to be in the ATP-binding domain of the RING11/PSF2 protein. This is in contrast to the mutant .134 (ref. 15), which lacks the RING4/PSF1 protein.
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second proteasome related gene in the human mhc class ii region
Nature, 1991Co-Authors: Adrian Kelly, Stephen H Powis, Richard Glynne, Elizabeth Radley, Stephan Beck, John TrowsdaleAbstract:Antgen processing involves the generation of peptides from cytosolic proteins and their transport into the endoplasmic reticulum where they associate with major histocompatibility complex (MHC) class I molecules. Two genes have been identified in the MHC class II region, RING4 and RING11 in humans, which are believed to encode the peptide transport proteins. Attention is now focused on how the transporters are provided with peptides. The proteasome, a large complex of subunits with multiple proteolytic activities, is a candidate for this function. Recently we reported a proteasome-related sequence, RING10, mapping between the transporter genes. Here we describe a second human proteasome-like gene, RING12, immediately centromeric of the RING4 locus. Therefore RING12, 4, 10 and 11 form a tightly linked cluster of interferon-inducible genes within the MHC with an essential role in antigen processing.
Carmen Sanchez - One of the best experts on this subject based on the ideXlab platform.
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rybp represses endogenous retroviruses and preimplantation and germ line specific genes in mouse embryonic stem cells
Molecular and Cellular Biology, 2012Co-Authors: Kaori Hisada, Haruhiko Koseki, Takaho A. Endo, Carmen Sanchez, Mitsuhiro Endoh, Monica Romantrufero, Jafar Sharif, Miguel VidalAbstract:Polycomb repressive complexes (PRCs) are important chromatin regulators of embryonic stem (ES) cell function. RYBP binds Polycomb H2A monoubiquitin ligases RING1A and RING1B and has been suggested to assist PRC localization to their targets. Moreover, constitutive inactivation of RYBP precludes ES cell formation. Using ES cells conditionally deficient in RYBP, we found that RYBP is not required for maintenance of the ES cell state, although mutant cells differentiate abnormally. Genome-wide chromatin association studies showed RYBP binding to promoters of Polycomb targets, although its presence is dispensable for gene repression. We discovered, using Eed-knockout (KO) ES cells, that RYBP binding to promoters was independent of H3K27me3. However, recruiting of PRC1 subunits RING1B and Mel18 to their targets was not altered in the absence of RYBP. In contrast, we have found that RYBP efficiently represses endogenous retroviruses (murine endogenous retrovirus [MuERV] class) and preimplantation (including zygotic genome activation stage)- and germ line-specific genes. These observations support a selective repressor activity for RYBP that is dispensable for Polycomb function in the ES cell state. Also, they suggest a role for RYBP in epigenetic resetting during preimplantation development through repression of germ line genes and PcG targets before formation of pluripotent epiblast cells.
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homeotic transformations of the axial skeleton of yy1 mutant mice and genetic interaction with the polycomb group gene RING1 RING1a
Mechanisms of Development, 2006Co-Authors: Mar Lorente, Claudia Perez, Carmen Sanchez, Mary E Donohoe, Yang Shi, Miguel VidalAbstract:Polycomb group (PcG) proteins participate in the maintenance of transcriptionally repressed state of genes relevant to cell differentiation. Here, we show anterior homeotic transformations of the axial skeleton of YY1(+/-) mice. We find that the penetrance of some of these alterations was reduced in mice that are deficient in the class II PcG gene RING1/RING1A, indicating a genetic interaction between those two genes. Further support for this interaction is an abnormal anterior eye formation in RING1-deficient mice, which is enhanced in compound YY1(+/-)RING1(-/-) mice. In addition, YY1 forms complexes with RING1 and other class II PcG proteins such as Rnf2 and Bmi1 in GST pull down experiments in transfected cells. These findings provide evidence for a PcG function for YY1 in vertebrates.
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homeotic transformations of the axial skeleton of yy1 mutant mice and genetic interaction with the polycomb group gene RING1 RING1a
Mechanisms of Development, 2006Co-Authors: Mar Lorente, Claudia Perez, Carmen Sanchez, Mary E Donohoe, Miguel VidalAbstract:Polycomb group (PcG) proteins participate in the maintenance of transcriptionally repressed state of genes relevant to cell differentiation. Here, we show anterior homeotic transformations of the axial skeleton of YY1 C/K mice. We find that the penetrance of some of these alterations was reduced in mice that are deficient in the class II PcG gene RING1/RING1A, indicating a genetic interaction between those two genes. Further support for this interaction is an abnormal anterior eye formation in RING1-deficient mice, which is enhanced in compound YY1 C/K RING1 K/K mice. In addition, YY1 forms complexes with RING1 and other class II PcG proteins such as Rnf2 and Bmi1 in GST pull down experiments in transfected cells. These findings provide evidence for a PcG function for YY1 in vertebrates. q 2006 Elsevier Ireland Ltd. All rights reserved.
Mar Lorente - One of the best experts on this subject based on the ideXlab platform.
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homeotic transformations of the axial skeleton of yy1 mutant mice and genetic interaction with the polycomb group gene RING1 RING1a
Mechanisms of Development, 2006Co-Authors: Mar Lorente, Claudia Perez, Carmen Sanchez, Mary E Donohoe, Yang Shi, Miguel VidalAbstract:Polycomb group (PcG) proteins participate in the maintenance of transcriptionally repressed state of genes relevant to cell differentiation. Here, we show anterior homeotic transformations of the axial skeleton of YY1(+/-) mice. We find that the penetrance of some of these alterations was reduced in mice that are deficient in the class II PcG gene RING1/RING1A, indicating a genetic interaction between those two genes. Further support for this interaction is an abnormal anterior eye formation in RING1-deficient mice, which is enhanced in compound YY1(+/-)RING1(-/-) mice. In addition, YY1 forms complexes with RING1 and other class II PcG proteins such as Rnf2 and Bmi1 in GST pull down experiments in transfected cells. These findings provide evidence for a PcG function for YY1 in vertebrates.
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homeotic transformations of the axial skeleton of yy1 mutant mice and genetic interaction with the polycomb group gene RING1 RING1a
Mechanisms of Development, 2006Co-Authors: Mar Lorente, Claudia Perez, Carmen Sanchez, Mary E Donohoe, Miguel VidalAbstract:Polycomb group (PcG) proteins participate in the maintenance of transcriptionally repressed state of genes relevant to cell differentiation. Here, we show anterior homeotic transformations of the axial skeleton of YY1 C/K mice. We find that the penetrance of some of these alterations was reduced in mice that are deficient in the class II PcG gene RING1/RING1A, indicating a genetic interaction between those two genes. Further support for this interaction is an abnormal anterior eye formation in RING1-deficient mice, which is enhanced in compound YY1 C/K RING1 K/K mice. In addition, YY1 forms complexes with RING1 and other class II PcG proteins such as Rnf2 and Bmi1 in GST pull down experiments in transfected cells. These findings provide evidence for a PcG function for YY1 in vertebrates. q 2006 Elsevier Ireland Ltd. All rights reserved.
