The Xenopus homologue of Down syndrome critical region protein 6 drives dorsoanterior gene expression and embryonic axis formation by antagonising polycomb group proteins

Development ◽  
2013 ◽  
Vol 140 (24) ◽  
pp. 4903-4913 ◽  
Author(s):  
H.-Y. Li ◽  
R. Grifone ◽  
A. Saquet ◽  
C. Carron ◽  
D.-L. Shi
Keyword(s):  
Gene Expression ◽  
Down Syndrome ◽  
Critical Region ◽  
Embryonic Axis ◽  
Polycomb Group ◽  
Axis Formation ◽  
Polycomb Group Proteins

scholarly journals Molecular characterisation of the Polycomblike gene of Drosophila melanogaster, a trans-acting negative regulator of homeotic gene expression

Development ◽  
1994 ◽  
Vol 120 (9) ◽  
pp. 2629-2636 ◽  
Author(s):  
A. Lonie ◽  
R. D'Andrea ◽  
R. Paro ◽  
R. Saint
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Polycomb Group ◽  
Negative Regulator ◽  
Homeotic Gene ◽  
Homeotic Genes ◽  
Molecular Characterisation ◽  
Polycomb Group Proteins ◽  
Polycomb Group Genes ◽  
Homeotic Gene Expression

The Polycomblike gene of Drosophila melanogaster, a member of the Polycomb Group of genes, is required for the correct spatial expression of the homeotic genes of the Antennapaedia and Bithorax Complexes. Mutations in Polycomb Group genes result in ectopic homeotic gene expression, indicating that Polycomb Group proteins maintain the transcriptional repression of specific homeotic genes in specific tissues during development. We report here the isolation and molecular characterisation of the Polycomblike gene. The Polycomblike transcript encodes an 857 amino acid protein with no significant homology to other proteins. Antibodies raised against the product of this open reading frame were used to show that the Polycomblike protein is found in all nuclei during embryonic development. Antibody staining also revealed that the Polycomblike protein is found on larval salivary gland polytene chromosomes at about 100 specific loci, the same loci to which the Polycomb and polyhomeotic proteins, two other Polycomb Group proteins, are found. These data add further support for a model in which Polycomb Group proteins form multimeric protein complexes at specific chromosomal loci to repress transcription at those loci.

scholarly journals Global differential expression of genes located in the Down Syndrome Critical Region in normal human brain

2014 ◽  
pp. 154-161 ◽  
Author(s):  
Julio Cesar Montoya ◽  
Dianora Fajardo ◽  
Ángela Peña ◽  
Adalberto Sánchez ◽  
Martha C Domínguez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Down Syndrome ◽  
Human Brain ◽  
Critical Region ◽  
Expression Profiles ◽  
Brain Atlas ◽  
Normal Human Brain ◽  
Normal Human ◽  
The Brain ◽  
Brain Homeostasis

Background: The information of gene expression obtained from databases, have made possible the extraction and analysis of data related with several molecular processes involving not only in brain homeostasis but its disruption in some neuropathologies; principally in Down syndrome and the Alzheimer disease. Objective: To correlate the levels of transcription of 19 genes located in the Down Syndrome Critical Region (DSCR) with their expression in several substructures of normal human brain. Methods: There were obtained expression profiles of 19 DSCR genes in 42 brain substructures, from gene expression values available at the database of the human brain of the Brain Atlas of the Allen Institute for Brain Sciences", (http://human.brain-map.org/). The co-expression patterns of DSCR genes in brain were calculated by using multivariate statistical methods. Results: Highest levels of gene expression were registered at caudate nucleus, nucleus accumbens and putamen among central areas of cerebral cortex. Increased expression levels of RCAN1 that encode by a protein involved in signal transduction process of the CNS were recorded for PCP4 that participates in the binding to calmodulin and TTC3; a protein that is associated with differentiation of neurons. That previously idenjpgied brain structures play a crucial role in the learning process, in different class of memory and in motor skills. Conclusion: The precise regulation of DSCR gene expression is crucial to maintain the brain homeostasis, especially in those areas with high levels of gene expression associated with a remarkable process of learning and cognition.

The Polycomb group in Caenorhabditis elegans and maternal control of germline development

Development ◽  
1998 ◽  
Vol 125 (13) ◽  
pp. 2469-2478 ◽  
Author(s):  
I. Korf ◽  
Y. Fan ◽  
S. Strome
Keyword(s):  
Gene Expression ◽  
Caenorhabditis Elegans ◽  
Polycomb Group ◽  
Polycomb Group Proteins ◽  
Polycomb Group Protein ◽  
Maternal Control ◽  
Germline Development ◽  
C Elegans ◽  
Polycomb Group Genes ◽  
Group Protein

Four Caenorhabditis elegans genes, mes-2, mes-3, mes-4 and mes-6, are essential for normal proliferation and viability of the germline. Mutations in these genes cause a maternal-effect sterile (i.e. mes) or grandchildless phenotype. We report that the mes-6 gene is in an unusual operon, the second example of this type of operon in C. elegans, and encodes the nematode homolog of Extra sex combs, a WD-40 protein in the Polycomb group in Drosophila. mes-2 encodes another Polycomb group protein (see paper by Holdeman, R., Nehrt, S. and Strome, S. (1998). Development 125, 2457–2467). Consistent with the known role of Polycomb group proteins in regulating gene expression, MES-6 is a nuclear protein. It is enriched in the germline of larvae and adults and is present in all nuclei of early embryos. Molecular epistasis results predict that the MES proteins, like Polycomb group proteins in Drosophila, function as a complex to regulate gene expression. Database searches reveal that there are considerably fewer Polycomb group genes in C. elegans than in Drosophila or vertebrates, and our studies suggest that their primary function is in controlling gene expression in the germline and ensuring the survival and proliferation of that tissue.

Programming of gene expression by Polycomb group proteins

2008 ◽  
Vol 18 (5) ◽  
pp. 236-243 ◽  
Author(s):  
Claudia Köhler ◽  
Corina B.R. Villar
Keyword(s):  
Gene Expression ◽  
Polycomb Group ◽  
Polycomb Group Proteins

Nuclear Factor of Activated T Cells Regulates Down Syndrome Critical Region 1 Gene Expression in Megakaryocytes.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1193-1193
Author(s):  
Satu Kyttaelae ◽  
Ivonne Habermann ◽  
Takashi Minami ◽  
Gerhard Ehninger ◽  
Alexander Kiani
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Down Syndrome ◽  
Cell Lines ◽  
Critical Region ◽  
Activated T Cells ◽  
Megakaryoblastic Leukemia ◽  
Cd34 Cells ◽  
Nfat Activation ◽  
Megakaryocytic Cell

Abstract The calcineurin-dependent NFAT (Nuclear Factors of Activated T cells) transcription factors were initially characterized as central mediators of inducible gene expression in activated T cells, but recently have also been implicated in regulating differentiation and function of a number of cell types outside the immune system. We have previously found that one member of the NFAT family, NFATc2, is strongly expressed in bone marrow megakaryocytes. The function of NFAT in this cell type, however, is unclear. The Down Syndrome Critical Region 1 (DSCR1) gene, located within the Down syndrome critical region of human chromosome 21, is overexpressed about 1,5-fold in patients with Down syndrome (DS) and has been implicated in the pathology of the disease. DSCR1 is a member of the calcipressin family of calcineurin inhibitors, and thereby serves as an endogenous suppressor of NFAT signalling. Furthermore, the expression of a specific isoform of the DSCR1 gene (exons 4–7) is thought to be regulated by NFAT, thus creating a potential regulatory feedback mechanism. Given the strong expression of NFATc2 in megakaryocytes, the complex interaction between DSCR1 and NFAT proteins, and the fact that DS children have a ~500-fold increased incidence of acute megakaryoblastic leukemia, we set out to analyze the expression and regulation of NFAT and DSCR1 in megakaryopoiesis. Pure populations of culture-derived (CD) megakaryocytes were obtained by culturing leukapheresis CD34+ cells in the presence of thrombopoietin. Using the calcium ionophor ionomycin and the calcineurin inhibitor cyclosporin A (CsA) in CD megakaryocytes as well as in various megakaryocytic cell lines, NFAT activation was found to be regulated in the same calcineurin-dependent and CsA-sensitive manner as is known from T lymphocytes. During the differentiation of CD34+ cells into megakaryocytes, the expression of NFATc2 protein was maintained at a high level, and progressive dephosphorylation of the protein in the course of the culture indicated activation of NFATc2 during the differentiation process. DSCR1 mRNA expression in CD34+ cells was low, but markedly upregulated during megakaryopoiesis. This upregulation was inhibited when differentiation was performed in the presence of CsA, an inhibitor of NFAT activation. In mature CD megakaryocytes as well as in all megakaryocytic cell lines tested, the expression of DSCR1 was further inducable by stimulating the cells with ionomycin and inhibited by treatment with CsA. To test the involvement of NFAT in the transcriptional regulation of the DSCR1 gene in megakaryocytes, CMK cell lines stably overexpressing either NFATc2 or the specific peptide inhibitor of NFAT activation, VIVIT, were generated by retroviral transduction. Overexpression of NFATc2 potently augmented, while VIVIT suppressed DSCR1 promoter transcriptional activity, confirming transcriptional regulation of DSCR1 expression by NFAT. These results establish DSCR1 as a transcriptional target gene for NFAT in megakaryocytes. The upregulation of DSCR1 expression during megakaryopoiesis suggests a possible implication of DSCR1 in megakaryocytic differentiation and should encourage further investigation into the reciprocal roles of DSCR1 and NFAT in the development of megakaryoblastic leukemia in DS.

Direct biomechanical induction of endogenous calcineurin inhibitor Down Syndrome Critical Region-1 in cardiac myocytes

2002 ◽  
Vol 283 (2) ◽  
pp. H533-H539 ◽  
Author(s):  
Yanlin Wang ◽  
Gilles W. De Keulenaer ◽  
Ellen O. Weinberg ◽  
Suphi Muangman ◽  
Antonio Gualberto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Down Syndrome ◽  
Cardiac Myocytes ◽  
Critical Region ◽  
Calcineurin Inhibitor ◽  
Critical Role ◽  
Mechanical Strain ◽  
Pressure Overload ◽  
Neonatal Rat ◽  
Dependent Manner

Signaling through the protein phosphatase calcineurin may play a critical role in cardiac hypertrophy. The gene for Down Syndrome Critical Region-1 (DSCR1) encodes a protein that is an endogenous calcineurin inhibitor. This study was designed to test the hypothesis that DSCR1 is directly induced by biomechanical stimuli. Neonatal rat cardiac myocytes were exposed to biaxial cyclic mechanical strain; mechanical strain upregulated DSCR1 mRNA expression in a time- and amplitude-dependent manner (3.4 ± 0.2-fold at 8% strain for 6 h, n = 11, P < 0.01), and this induction was angiotensin II and endothelin I independent. Biomechanical induction of DSCR1 mRNA was partially blocked by calcineurin inhibition with cyclosporine A (30 ± 5%, n = 3, P < 0.01). DSCR1 promoter-reporter experiments showed that mechanical strain induced DSCR1 promoter activity by 2.3-fold and that this induction was completely inhibited by cyclosporin A. Furthermore, DSCR1 gene expression was increased in the left ventricles of mice with pressure-overload hypertrophy induced by transverse aortic banding. These data demonstrate that biomechanical strain directly induces gene expression for the calcineurin inhibitor DSCR1 in cardiac myocytes, indicating that mechanically induced DSCR1 may regulate the hypertrophic response to mechanical overload.

Function of the Polycomb protein is conserved in mice and flies

Development ◽  
1995 ◽  
Vol 121 (9) ◽  
pp. 2847-2852 ◽  
Author(s):  
J. Muller ◽  
S. Gaunt ◽  
P.A. Lawrence
Keyword(s):  
Gene Expression ◽  
Molecular Mechanism ◽  
Polycomb Group ◽  
Polycomb Group Proteins ◽  
Cell Fates ◽  
Cell Determination ◽  
Mouse Homologue ◽  
Polycomb Protein ◽  
Selector Genes ◽  
Transgenic Flies

A key aspect of determination--the acquisition and propagation of cell fates--is the initiation of patterns of selector gene expression and their maintenance in groups of cells as they divide and develop. In Drosophila, in those groups of cells where particular selector genes must remain inactive, it is the Polycomb-Group of genes that keep them silenced. Here we show that M33, a mouse homologue of the Drosophila Polycomb protein, can substitute for Polycomb in transgenic flies. Polycomb protein is thought to join with other Polycomb-Group proteins to build a complex that silences selector genes. Since members of this group of proteins have their homologues in mice, our results suggest that the molecular mechanism of cell determination is widely conserved.

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