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KRAB-containing zinc-finger repressor proteins
Raul Urrutia
Genome Biology , 2003, DOI: 10.1186/gb-2003-4-10-231
Abstract: Zinc-finger proteins containing the Krüppel-associated box (KRAB-containing proteins) were discovered in 1991 by Bellefroid et al. [1]. They make up approximately one third (290) of the 799 different zinc-finger proteins present in the human genome, and as a result, this group of proteins is the largest single family of transcriptional regulators in mammals. Many genes encoding KRAB-containing proteins are arranged in clusters, but others occur individually throughout the genome. The best characterized cluster is on 19q, containing 148 genes (51% of the family) within a region close to 19q13 [2]; other clusters are in centromeric and telomeric regions of other chromosomes. In particular, members of the family containing SCAN domains (see below) are clustered on 3p21-22, 6p21-22, 16p13.3, and 17p12-13. Non-clustered genes encoding KRAB-containing proteins are scattered over the other chromosomes, with about half on autosomes and half on sex chromosomes. Although the expression of genes of other clustered families, such as homeobox genes, is coregulated, it remains to be determined whether a comparable mechanism operates for genes encoding KRAB-containing proteins, and more studies are needed to show how chromosome organization influences the expression patterns of this family.As shown in Figure 1, KRAB-containing proteins are characterized by the presence of a DNA-binding domain made up of between 4 and over 30 zinc-finger motifs and a KRAB domain. The KRAB domain, located near the amino terminus of the protein, consists of one or both of the KRAB A box and the KRAB B box (see below). Other domains, such as the SCAN domain, are found in a small subset of members of the family [2,3] (Table 1). The two boxes of the KRAB domain are always encoded by individual exons separated by introns of variable sizes. This exon-intron composition allows the generation of different products by alternative splicing. In fact, zinc-finger proteins that contain only a KRAB A domain, for
The Heterochromatin Protein 1 family
Gwen Lomberk, Lori Wallrath, Raul Urrutia
Genome Biology , 2006, DOI: 10.1186/gb-2006-7-7-228
Abstract: Heterochromatin protein 1 (HP1) was originally discovered through studies in Drosophila of the mosaic gene silencing that results when a euchromatic gene is placed near or within heterochromatin, the condensed state of chromatin that is a cytologically visible condition of heritable gene repression [1,2]. This phenomenon is known as position-effect variegation (PEV), and HP1 is a dominant suppressor of it. The HP1 family of non-histone chromosomal proteins are involved in the establishment and maintenance of higher-order chromatin structures. Members of this evolutionarily conserved family have been discovered in almost all eukaryotic organisms, from fission yeast to plants to humans (Figure 1). An HP1 protein has not been observed in budding yeast (Saccharomyces cerevisiae), in which PEV is generated by the silent information regulatory (SIR) proteins [3]. The fission yeast (Schizosaccharomyces pombe) and Neurospora genomes each contain one HP1 homolog, Dictyostelium has two, and different animal species have up to five. Over the length of the protein, there is 50% amino-acid sequence identity between mammalian HP1 proteins and Drosophila HP1 [4].The HP1 family of proteins is encoded by a class of genes known as the chromobox (CBX) genes. There are three distinct proteins in the mammalian HP1 family, each of which is encoded by its own gene. In humans, HP1α is encoded by the Chromobox homolog 5 (CBX5) gene located on chromosome 12q13.13 [5]. The genes for HP1β (CBX1) and HP1γ (CBX3) are located on chromosomes 17q21.32 and 7p15.2, respectively. The murine Cbx5, Cbx1 and Cbx3 genes are located within syntenic regions of the mouse genome to the orthologous human genes: 15qF3, 11qD and 6qB3, respectively [6]. This conserved synteny shows that HP1 proteins have evolved under stringent evolutionary pressures, indicating that their function has been carefully selected. CBX5, CBX1 and CBX3 encode proteins with distinct localization patterns, however, despite being approxim
Sp1- and Krüppel-like transcription factors
Joanna Kaczynski, Tiffany Cook, Raul Urrutia
Genome Biology , 2003, DOI: 10.1186/gb-2003-4-2-206
Abstract: Sp1 was identified in the early 1980s and was one of the first transcription factors to be purified and cloned from, and characterized in, mammalian cells [1,2]. Sp1 was shown to recognize and specifically bind to GC-rich sites within the simian virus 40 (SV40) promoter via three Cys2His2 zinc-finger motifs. A similar DNA-binding domain had been found in many developmental regulators, including the Drosophila embryonic pattern regulator Krüppel [2]. Subsequently, other transcription factors were identified that had zinc-finger motifs highly similar to those of Sp1, thereby defining a novel class of Sp1-like proteins or Krüppel-like factors (KLFs) [3,4,5,6,7,8,9]. Because many members of the Sp1-like/KLF family have acquired multiple names over time, the nomenclature for these proteins is currently being revised and standardized. In this article, we follow the current nomenclature of Sp1-Sp6, with the remainder of the family called KLFs, and we refer to other names of each protein on first mention.Sp1-like/KLF proteins are present in species ranging from the nematode Caenorhabditis elegans to humans and appear to have evolved through multiple gene-duplication events [10,11,12,13,14]. The fruitfly, for instance, has three Sp1-like proteins [12,13], whereas up to 21 Sp1-like/KLF genes have been identified in humans by a variety of cloning approaches. So far, homologs of 17 of the 21 human Sp1-like/KLF proteins have been found in mouse, and 11 have been found in rat. Other species, such as zebrafish, have fewer members of the Sp1-like family (Table 1). To date, no systematic comparisons have been made of the structural and functional properties of Sp1-like/KLF proteins in humans and other species.Like Sp1, factors of the Sp1-like/KLF family can bind various GC-rich DNA elements and regulate transcription. Furthermore, many Sp1-like transcription factors both in mammals and in invertebrates are involved in processes regulating cell growth and control morphogenetic pathwa
MAGE I Transcription Factors Regulate KAP1 and KRAB Domain Zinc Finger Transcription Factor Mediated Gene Repression
Tony Z. Xiao, Neehar Bhatia, Raul Urrutia, Gwen A. Lomberk, Andrew Simpson, B. Jack Longley
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0023747
Abstract: Class I MAGE proteins (MAGE I) are normally expressed only in developing germ cells but are aberrantly expressed in many cancers. They have been shown to promote tumor survival, aggressive growth, and chemoresistance but the underlying mechanisms and MAGE I functions have not been fully elucidated. KRAB domain zinc finger transcription factors (KZNFs) are the largest group of vertebrate transcription factors and regulate neoplastic transformation, tumor suppression, cellular proliferation, and apoptosis. KZNFs bind the KAP1 protein and direct KAP1 to specific DNA sequences where it suppresses gene expression by inducing localized heterochromatin characterized by histone 3 lysine 9 trimethylation (H3me3K9). Discovery that MAGE I proteins also bind to KAP1 prompted us to investigate whether MAGE I can affect KZNF and KAP1 mediated gene regulation. We found that expression of MAGE I proteins, MAGE-A3 or MAGE-C2, relieved repression of a reporter gene by ZNF382, a KZNF with tumor suppressor activity. ChIP of MAGE I (-) HEK293T cells showed KAP1 and H3me3K9 are normally bound to the ID1 gene, a target of ZNF382, but that binding is greatly reduced in the presence of MAGE I proteins. MAGE I expression relieved KAP1 mediated ID1 repression, causing increased expression of ID1 mRNA and ID1 chromatin relaxation characterized by loss of H3me3K9. MAGE I binding to KAP1 also induced ZNF382 poly-ubiquitination and degradation, consistent with loss of ZNF382 leading to decreased KAP1 binding to ID1. In contrast, MAGE I expression caused increased KAP1 binding to Ki67, another KAP1 target gene, with increased H3me3K9 and decreased Ki67 mRNA expression. Since KZNFs are required to direct KAP1 to specific genes, these results show that MAGE I proteins can differentially regulate members of the KZNF family and KAP1 mediated gene repression.
One-Dimensional Photonic Heterostructure with Broadband Omnidirectional Reflection
Jesus Manzanares-Martinez;Raul Archuleta-Garcia;Paola Castro-Garay;Damian Moctezuma-Enriquez;Efrain Urrutia-Banuelos
PIER , 2011, DOI: 10.2528/PIER10110404
Abstract: In this work we report the modeling of an one-dimensional photonic heterostructure which presents a giant omnidirectional photonic band gap. This omnidirectional reflector is made by the union of lattices with the same filling fraction and index contrast, but with different lattice periods. Using the scalability of the electromagnetic wave equation we present a simple manner to enlarge ---as large as desired--- the omnidirectional mirror. We apply our method to design an omnidirectional reflector for all the visible range.
Designing a Nano Infrastructure for Brazil’s Amazon Water Resources: A Quadruple Helix Approach  [PDF]
Raul Gouvea
Journal of Water Resource and Protection (JWARP) , 2015, DOI: 10.4236/jwarp.2015.71005
Abstract: This paper elaborates on the role of green technologies and innovations in “greening” Brazil’s Amazon region fresh water resources. The paper elaborates on the development of an innovation quadruple helix to better manage the region’s water resources. Brazil accounts for close to 12% of the earth’s fresh water reserves, while most of it is in the Amazon region. The preservation of water reserves on a global scale is of paramount importance in the 21st century. Brazil, however, has not managed its water resources effectively leading to the increasing pollution and contamination of its Amazonian water resources.
A Novel Role of the Sp/KLF Transcription Factor KLF11 in Arresting Progression of Endometriosis
Gaurang S. Daftary, Ye Zheng, Zaid M. Tabbaa, John K. Schoolmeester, Ravi P. Gada, Adrienne L. Grzenda, Angela J. Mathison, Gary L. Keeney, Gwen A. Lomberk, Raul Urrutia
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0060165
Abstract: Endometriosis affects approximately 10% of young, reproductive-aged women. Disease associated pelvic pain; infertility and sexual dysfunction have a significant adverse clinical, social and financial impact. As precise disease etiology has remained elusive, current therapeutic strategies are empiric, unfocused and often unsatisfactory. Lack of a suitable genetic model has impaired further translational research in the field. In this study, we evaluated the role of the Sp/KLF transcription factor KLF11/Klf11 in the pathogenesis of endometriosis. KLF11, a human disease-associated gene is etiologically implicated in diabetes, uterine fibroids and cancer. We found that KLF11 expression was diminished in human endometriosis implants and further investigated its pathogenic role in Klf11-/- knockout mice with surgically induced endometriotic lesions. Lesions in Klf11-/- animals were large and associated with prolific fibrotic adhesions resembling advanced human disease in contrast to wildtype controls. To determine phenotype-specificity, endometriosis was also generated in Klf9-/- animals. Unlike in Klf11-/- mice, lesions in Klf9-/- animals were neither large, nor associated with a significant fibrotic response. KLF11 also bound to specific elements located in the promoter regions of key fibrosis-related genes from the Collagen, MMP and TGF-β families in endometrial stromal cells. KLF11 binding resulted in transcriptional repression of these genes. In summary, we identify a novel pathogenic role for KLF11 in preventing de novo disease-associated fibrosis in endometriosis. Our model validates in vivo the phenotypic consequences of dysregulated Klf11 signaling. Additionally, it provides a robust means not only for further detailed mechanistic investigation but also the ability to test any emergent translational ramifications thereof, so as to expand the scope and capability for treatment of endometriosis.
Los eslabonamientos y la historia económica de Colombia
Desarrollo y Sociedad , 2008,
Abstract: the paper analyzes albert hirschman′s theory of linkages in economic development in his writings, and the possible influence of his colombia experience in the development of this idea. the theory is then applied to explain colombia's economic history in the nineteenth and twentieth century.
Hacia una política en tránsito: Ficción en el cine chileno (2008-2010)
Aisthesis , 2010, DOI: 10.4067/S0718-71812010000100003
Abstract: cinema is political in the sense that film camera never takes a neutral position and it always manages to establish a dialog with its social and cultural environment. in fact, although chilean contemporary fiction dissociates itself from any explicit ideological discourse due to its primary focus on intimacy and everyday life, its alienated representation of life turns into a purely political feeling of unease and uncertainty.
Script, un modelo cognitivo del lenguaje.: Estudio experimental a partir de tres grupos etáreos
Revista signos , 2004, DOI: 10.4067/S0718-09342004005500005
Abstract: this article gives account of an experimental research that consists of outlining the structure and functioning of possible forms of organization of human knowledge, from a script of a visit to the doctor's. the corpus consists of oral reports transcribed that give an account of the experiences of the subjects of study when visiting the doctor's. the subjects are divided in three age groups: 10 young people, 10 adults and 10 elder people of michaihue, an area in san pedro de la paz, in concepcion. the results obtained contribute to the information about the way in which these scripts are stored in the human memory, the different linguistics tendencies among the number of events and peripheral ways, according to their age; and the way in which these mental constructs, scripts, leave an imprint in future actions of human experience, as it has been observed in this experience with users of chilean public health service.
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