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Pesquisa : G05.728.615.475 [Categoria DeCS]
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[PMID]:28743762
[Au] Autor:Hum YF; Jinks-Robertson S
[Ad] Endereço:Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina 27710.
[Ti] Título:Mitotic Gene Conversion Tracts Associated with Repair of a Defined Double-Strand Break in .
[So] Source:Genetics;207(1):115-128, 2017 09.
[Is] ISSN:1943-2631
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mitotic recombination between homologous chromosomes leads to the uncovering of recessive alleles through loss of heterozygosity. In the current study, a defined double-strand break was used to initiate reciprocal loss of heterozygosity between diverged homologs of chromosome IV in These events resulted from the repair of two broken chromatids, one of which was repaired as a crossover and the other as a noncrossover. Associated gene conversion tracts resulting from the donor-directed repair of mismatches formed during strand exchange (heteroduplex DNA) were mapped using microarrays. Gene conversion tracts associated with individual crossover and noncrossover events were similar in size and position, with half of the tracts being unidirectional and mapping to only one side of the initiating break. Among crossover events, this likely reflected gene conversion on only one side of the break, with restoration-type repair occurring on the other side. For noncrossover events, an ectopic system was used to directly compare gene conversion tracts produced in a wild-type strain to heteroduplex DNA tracts generated in the absence of the Mlh1 mismatch-repair protein. There was a strong bias for unidirectional tracts in the absence, but not in the presence, of Mlh1 This suggests that mismatch repair acts on heteroduplex DNA that is only transiently present in noncrossover intermediates of the synthesis dependent strand annealing pathway. Although the molecular features of events associated with loss of heterozygosity generally agreed with those predicted by current recombination models, there were unexpected complexities in associated gene conversion tracts.
[Mh] Termos MeSH primário: Quebras de DNA de Cadeia Dupla
Conversão Gênica
Mitose/genética
Reparo de DNA por Recombinação
Saccharomyces cerevisiae/genética
[Mh] Termos MeSH secundário: Troca Genética
Saccharomyces cerevisiae/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.1534/genetics.117.300057


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[PMID]:28977405
[Au] Autor:van der Lee R; Wiel L; van Dam TJP; Huynen MA
[Ad] Endereço:Centre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
[Ti] Título:Genome-scale detection of positive selection in nine primates predicts human-virus evolutionary conflicts.
[So] Source:Nucleic Acids Res;45(18):10634-10648, 2017 Oct 13.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Hotspots of rapid genome evolution hold clues about human adaptation. We present a comparative analysis of nine whole-genome sequenced primates to identify high-confidence targets of positive selection. We find strong statistical evidence for positive selection in 331 protein-coding genes (3%), pinpointing 934 adaptively evolving codons (0.014%). Our new procedure is stringent and reveals substantial artefacts (20% of initial predictions) that have inflated previous estimates. The final 331 positively selected genes (PSG) are strongly enriched for innate and adaptive immunity, secreted and cell membrane proteins (e.g. pattern recognition, complement, cytokines, immune receptors, MHC, Siglecs). We also find evidence for positive selection in reproduction and chromosome segregation (e.g. centromere-associated CENPO, CENPT), apolipoproteins, smell/taste receptors and mitochondrial proteins. Focusing on the virus-host interaction, we retrieve most evolutionary conflicts known to influence antiviral activity (e.g. TRIM5, MAVS, SAMHD1, tetherin) and predict 70 novel cases through integration with virus-human interaction data. Protein structure analysis further identifies positive selection in the interaction interfaces between viruses and their cellular receptors (CD4-HIV; CD46-measles, adenoviruses; CD55-picornaviruses). Finally, primate PSG consistently show high sequence variation in human exomes, suggesting ongoing evolution. Our curated dataset of positive selection is a rich source for studying the genetics underlying human (antiviral) phenotypes. Procedures and data are available at https://github.com/robinvanderlee/positive-selection.
[Mh] Termos MeSH primário: Evolução Molecular
Seleção Genética
[Mh] Termos MeSH secundário: Animais
Artefatos
Conversão Gênica
Variação Genética
Genômica
Interações Hospedeiro-Patógeno/genética
Seres Humanos
Imunidade/genética
Família Multigênica
Primatas/genética
Proteínas/genética
Receptores Virais/química
Proteínas Virais/química
Viroses/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Proteins); 0 (Receptors, Virus); 0 (Viral Proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171005
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx704


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[PMID]:28846694
[Au] Autor:Skov L; Schierup MH; Danish Pan Genome Consortium
[Ad] Endereço:Bioinformatics Research Centre, Aarhus University, Aarhus C., Denmark.
[Ti] Título:Analysis of 62 hybrid assembled human Y chromosomes exposes rapid structural changes and high rates of gene conversion.
[So] Source:PLoS Genet;13(8):e1006834, 2017 Aug.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The human Y-chromosome does not recombine across its male-specific part and is therefore an excellent marker of human migrations. It also plays an important role in male fertility. However, its evolution is difficult to fully understand because of repetitive sequences, inverted repeats and the potentially large role of gene conversion. Here we perform an evolutionary analysis of 62 Y-chromosomes of Danish descent sequenced using a wide range of library insert sizes and high coverage, thus allowing large regions of these chromosomes to be well assembled. These include 17 father-son pairs, which we use to validate variation calling. Using a recent method that can integrate variants based on both mapping and de novo assembly, we genotype 10898 SNVs and 2903 indels (max length of 27241 bp) in our sample and show by father-son concordance and experimental validation that the non-recurrent SNP and indel variation on the Y chromosome tree is called very accurately. This includes variation called in a 0.9 Mb centromeric heterochromatic region, which is by far the most variable in the Y chromosome. Among the variation is also longer sequence-stretches not present in the reference genome but shared with the chimpanzee Y chromosome. We analyzed 2.7 Mb of large inverted repeats (palindromes) for variation patterns among the two palindrome arms and identified 603 mutation and 416 gene conversions events. We find clear evidence for GC-biased gene conversion in the palindromes (and a balancing AT mutation bias), but irrespective of this, also a strong bias towards gene conversion towards the ancestral state, suggesting that palindromic gene conversion may alleviate Muller's ratchet. Finally, we also find a large number of large-scale gene duplications and deletions in the palindromic regions (at least 24) and find that such events can consist of complex combinations of simultaneous insertions and deletions of long stretches of the Y chromosome.
[Mh] Termos MeSH primário: Cromossomos Humanos Y/genética
Evolução Molecular
Heterocromatina/genética
Mutação INDEL/genética
[Mh] Termos MeSH secundário: Dinamarca
Pai
Conversão Gênica/genética
Seres Humanos
Infertilidade Masculina/genética
Infertilidade Masculina/patologia
Sequências Repetidas Invertidas/genética
Masculino
Núcleo Familiar
Filogenia
Polimorfismo de Nucleotídeo Único
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Heterochromatin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171011
[Lr] Data última revisão:
171011
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006834


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[PMID]:28727785
[Au] Autor:Champer J; Reeves R; Oh SY; Liu C; Liu J; Clark AG; Messer PW
[Ad] Endereço:Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, United States of America.
[Ti] Título:Novel CRISPR/Cas9 gene drive constructs reveal insights into mechanisms of resistance allele formation and drive efficiency in genetically diverse populations.
[So] Source:PLoS Genet;13(7):e1006796, 2017 07.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A functioning gene drive system could fundamentally change our strategies for the control of vector-borne diseases by facilitating rapid dissemination of transgenes that prevent pathogen transmission or reduce vector capacity. CRISPR/Cas9 gene drive promises such a mechanism, which works by converting cells that are heterozygous for the drive construct into homozygotes, thereby enabling super-Mendelian inheritance. Although CRISPR gene drive activity has already been demonstrated, a key obstacle for current systems is their propensity to generate resistance alleles, which cannot be converted to drive alleles. In this study, we developed two CRISPR gene drive constructs based on the nanos and vasa promoters that allowed us to illuminate the different mechanisms by which resistance alleles are formed in the model organism Drosophila melanogaster. We observed resistance allele formation at high rates both prior to fertilization in the germline and post-fertilization in the embryo due to maternally deposited Cas9. Assessment of drive activity in genetically diverse backgrounds further revealed substantial differences in conversion efficiency and resistance rates. Our results demonstrate that the evolution of resistance will likely impose a severe limitation to the effectiveness of current CRISPR gene drive approaches, especially when applied to diverse natural populations.
[Mh] Termos MeSH primário: Sistemas CRISPR-Cas/genética
Resistência à Doença/genética
Desenvolvimento Embrionário/genética
Genética Populacional
[Mh] Termos MeSH secundário: Alelos
Animais
Animais Geneticamente Modificados
Drosophila melanogaster/genética
Fertilização/genética
Conversão Gênica/genética
Células Germinativas
Mutação/genética
Transgenes/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170721
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006796


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[PMID]:28531201
[Au] Autor:Clément Y; Sarah G; Holtz Y; Homa F; Pointet S; Contreras S; Nabholz B; Sabot F; Sauné L; Ardisson M; Bacilieri R; Besnard G; Berger A; Cardi C; De Bellis F; Fouet O; Jourda C; Khadari B; Lanaud C; Leroy T; Pot D; Sauvage C; Scarcelli N; Tregear J; Vigouroux Y; Yahiaoui N; Ruiz M; Santoni S; Labouisse JP; Pham JL; David J; Glémin S
[Ad] Endereço:Montpellier SupAgro, UMR AGAP, Montpellier, France.
[Ti] Título:Evolutionary forces affecting synonymous variations in plant genomes.
[So] Source:PLoS Genet;13(5):e1006799, 2017 May.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Base composition is highly variable among and within plant genomes, especially at third codon positions, ranging from GC-poor and homogeneous species to GC-rich and highly heterogeneous ones (particularly Monocots). Consequently, synonymous codon usage is biased in most species, even when base composition is relatively homogeneous. The causes of these variations are still under debate, with three main forces being possibly involved: mutational bias, selection and GC-biased gene conversion (gBGC). So far, both selection and gBGC have been detected in some species but how their relative strength varies among and within species remains unclear. Population genetics approaches allow to jointly estimating the intensity of selection, gBGC and mutational bias. We extended a recently developed method and applied it to a large population genomic dataset based on transcriptome sequencing of 11 angiosperm species spread across the phylogeny. We found that at synonymous positions, base composition is far from mutation-drift equilibrium in most genomes and that gBGC is a widespread and stronger process than selection. gBGC could strongly contribute to base composition variation among plant species, implying that it should be taken into account in plant genome analyses, especially for GC-rich ones.
[Mh] Termos MeSH primário: Evolução Molecular
Genoma de Planta
Magnoliopsida/genética
Polimorfismo Genético
[Mh] Termos MeSH secundário: Sequência Rica em GC
Conversão Gênica
Seleção Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170523
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006799


  6 / 2375 MEDLINE  
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[PMID]:28502720
[Au] Autor:Lee W; Syed Atif A; Tan SC; Leow CH
[Ad] Endereço:Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), 11800 Minden, Penang, Malaysia.
[Ti] Título:Insights into the chicken IgY with emphasis on the generation and applications of chicken recombinant monoclonal antibodies.
[So] Source:J Immunol Methods;447:71-85, 2017 Aug.
[Is] ISSN:1872-7905
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The advantages of chicken (Gallus gallus domesticus) antibodies as immunodiagnostic and immunotherapeutic biomolecules has only been recently recognized. Even so, chicken antibodies remain less-well characterized than their mammalian counterparts. This review aims at providing a current overview of the structure, function, development and generation of chicken antibodies. Additionally, brief but comprehensive insights into current knowledge pertaining to the immunogenetic framework and diversity-generation of the chicken immunoglobulin repertoire which have contributed to the establishment of recombinant chicken mAb-generating methods are discussed. Focus is provided on the current methods used to generate antibodies from chickens with added emphasis on the generation of recombinant chicken mAbs and its derivative formats. The advantages and limitations of established protocols for the generation of chicken mAbs are highlighted. The various applications of recombinant chicken mAbs and its derivative formats in immunodiagnostics and immunotherapy are further detailed.
[Mh] Termos MeSH primário: Anticorpos Monoclonais
Galinhas/imunologia
Imunoglobulinas
[Mh] Termos MeSH secundário: Animais
Anticorpos Monoclonais/biossíntese
Anticorpos Monoclonais/química
Anticorpos Monoclonais/genética
Anticorpos Monoclonais/imunologia
Conversão Gênica
Imunoglobulinas/química
Imunoglobulinas/genética
Imunoglobulinas/imunologia
Testes Imunológicos/métodos
Imunoterapia
Proteínas Recombinantes/biossíntese
Proteínas Recombinantes/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (IgY); 0 (Immunoglobulins); 0 (Recombinant Proteins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170516
[St] Status:MEDLINE


  7 / 2375 MEDLINE  
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[PMID]:28400415
[Au] Autor:Ruhlman TA; Zhang J; Blazier JC; Sabir JSM; Jansen RK
[Ad] Endereço:Department of Integrative Biology, University of Texas at Austin, Austin, Texas 78712 USA truhlman@austin.utexas.edu.
[Ti] Título:Recombination-dependent replication and gene conversion homogenize repeat sequences and diversify plastid genome structure.
[So] Source:Am J Bot;104(4):559-572, 2017 Apr.
[Is] ISSN:1537-2197
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PREMISE OF THE STUDY: There is a misinterpretation in the literature regarding the variable orientation of the small single copy region of plastid genomes (plastomes). The common phenomenon of small and large single copy inversion, hypothesized to occur through intramolecular recombination between inverted repeats (IR) in a circular, single unit-genome, in fact, more likely occurs through recombination-dependent replication (RDR) of linear plastome templates. If RDR can be primed through both intra- and intermolecular recombination, then this mechanism could not only create inversion isomers of so-called single copy regions, but also an array of alternative sequence arrangements. METHODS: We used Illumina paired-end and PacBio single-molecule real-time (SMRT) sequences to characterize repeat structure in the plastome of (Geraniaceae). We used OrgConv and inspected nucleotide alignments to infer ancestral nucleotides and identify gene conversion among repeats and mapped long (>1 kb) SMRT reads against the unit-genome assembly to identify alternative sequence arrangements. RESULTS: Although lacks the canonical IR, we found that large repeats (>1 kilobase; kb) represent ∼22% of the plastome nucleotide content. Among the largest repeats (>2 kb), we identified GC-biased gene conversion and mapping filtered, long SMRT reads to the unit-genome assembly revealed alternative, substoichiometric sequence arrangements. CONCLUSION: We offer a model based on RDR and gene conversion between long repeated sequences in the plastome and provide support that both intra-and intermolecular recombination between large repeats, particularly in repeat-rich plastomes, varies unit-genome structure while homogenizing the nucleotide sequence of repeats.
[Mh] Termos MeSH primário: Conversão Gênica/genética
Genomas de Plastídeos/genética
Recombinação Genética/genética
[Mh] Termos MeSH secundário: Replicação do DNA/genética
Genoma de Planta/genética
Geraniaceae/genética
Sequências Repetitivas de Ácido Nucleico/genética
Alinhamento de Sequência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170822
[Lr] Data última revisão:
170822
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170413
[St] Status:MEDLINE
[do] DOI:10.3732/ajb.1600453


  8 / 2375 MEDLINE  
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[PMID]:28333217
[Au] Autor:Kursel LE; Malik HS
[Ad] Endereço:Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA.
[Ti] Título:Recurrent Gene Duplication Leads to Diverse Repertoires of Centromeric Histones in Drosophila Species.
[So] Source:Mol Biol Evol;34(6):1445-1462, 2017 Jun 01.
[Is] ISSN:1537-1719
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Despite their essential role in the process of chromosome segregation in most eukaryotes, centromeric histones show remarkable evolutionary lability. Not only have they been lost in multiple insect lineages, but they have also undergone gene duplication in multiple plant lineages. Based on detailed study of a handful of model organisms including Drosophila melanogaster, centromeric histone duplication is considered to be rare in animals. Using a detailed phylogenomic study, we find that Cid, the centromeric histone gene, has undergone at least four independent gene duplications during Drosophila evolution. We find duplicate Cid genes in D. eugracilis (Cid2), in the montium species subgroup (Cid3, Cid4) and in the entire Drosophila subgenus (Cid5). We show that Cid3, Cid4, and Cid5 all localize to centromeres in their respective species. Some Cid duplicates are primarily expressed in the male germline. With rare exceptions, Cid duplicates have been strictly retained after birth, suggesting that they perform nonredundant centromeric functions, independent from the ancestral Cid. Indeed, each duplicate encodes a distinct N-terminal tail, which may provide the basis for distinct protein-protein interactions. Finally, we show some Cid duplicates evolve under positive selection whereas others do not. Taken together, our results support the hypothesis that Drosophila Cid duplicates have subfunctionalized. Thus, these gene duplications provide an unprecedented opportunity to dissect the multiple roles of centromeric histones.
[Mh] Termos MeSH primário: Centrômero/genética
Proteínas de Ligação a DNA/genética
Proteínas de Drosophila/genética
Drosophila melanogaster/genética
Histonas/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Centrômero/metabolismo
Proteína Centromérica A
Evolução Molecular
Conversão Gênica/genética
Duplicação Gênica/genética
Histonas/metabolismo
Modelos Genéticos
Filogenia
Seleção Genética/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Centromere Protein A); 0 (Cid protein, Drosophila); 0 (DNA-Binding Proteins); 0 (Drosophila Proteins); 0 (Histones)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE
[do] DOI:10.1093/molbev/msx091


  9 / 2375 MEDLINE  
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[PMID]:28303348
[Au] Autor:Trombetta B; Cruciani F
[Ad] Endereço:Dipartimento di Biologia e Biotecnologie "Charles Darwin", Sapienza Università di Roma, Rome, Italy.
[Ti] Título:Y chromosome palindromes and gene conversion.
[So] Source:Hum Genet;136(5):605-619, 2017 May.
[Is] ISSN:1432-1203
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The presence of large and near-identical inverted repeat sequences (called palindromes) is a common feature of the constitutively haploid sex chromosomes of different species. Despite the fact palindromes originated in a non-recombining context, they have evolved a strong recombinational activity in the form of abundant arm-to-arm gene conversion. Their independent appearance in different species suggests they can have a profound biological significance that has yet to be fully clarified. It has been theorized that natural selection may have favored palindromic organization of male-specific genes and that the establishment of intra-palindrome gene conversion has strong adaptive significance. Arm-to-arm gene conversion allows the efficient removal of deleterious mutations, increases the fixation rate of beneficial mutations and has played an important role in modulating the equilibrium between gene loss and acquisition during Y chromosome evolution. Additionally, a palindromic organization of duplicates could favor the formation of unusual chromatin structures and could optimize the use of gene conversion as a mechanism to maintain the structural integrity of male-specific genes. In this review, we describe the structural features of palindromes on mammalian sex chromosomes and summarize different hypotheses regarding palindrome evolution and the functional benefits of arm-to-arm gene conversion on the unique haploid portion of the nuclear genome.
[Mh] Termos MeSH primário: Cromossomos Humanos Y/genética
Conversão Gênica
[Mh] Termos MeSH secundário: Instabilidade Cromossômica
Evolução Molecular
Genoma Humano
Seres Humanos
Sequências Repetidas Invertidas
Masculino
Mutação
Polimorfismo de Nucleotídeo Único
Análise de Sequência de DNA
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170318
[St] Status:MEDLINE
[do] DOI:10.1007/s00439-017-1777-8


  10 / 2375 MEDLINE  
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[PMID]:28301039
[Au] Autor:Budzynska PM; Kyläniemi MK; Kallonen T; Soikkeli AI; Nera KP; Lassila O; Alinikula J
[Ad] Endereço:Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
[Ti] Título:Bach2 regulates AID-mediated immunoglobulin gene conversion and somatic hypermutation in DT40 B cells.
[So] Source:Eur J Immunol;47(6):993-1001, 2017 Jun.
[Is] ISSN:1521-4141
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The transcription factor Bach2 is required for germinal center formation, somatic hypermutation (SHM), and class-switch recombination (CSR) of immunoglobulins. SHM and CSR are initiated by activation-induced cytidine deaminase (AID) which has potential to induce human B cell lymphoma. To understand the role of Bach2 in AID-mediated immunoglobulin gene diversification processes, we established a BACH2-deficient DT40 B cell line. We show that in addition to allowing SHM, Bach2 drives immunoglobulin gene conversion (GCV), another AID-dependent antibody gene diversification process. We demonstrate that Bach2 promotes GCV by increasing the expression of AID. Importantly, we found that the regulation of AID is independent of Blimp-1 and that BACH2-deficient cells have altered expression of several genes regulating AID expression, stability and function. Furthermore, re-expression of BACH2 or AID in Bach2KO cells restored the SHM and GCV defects. These results demonstrate that Bach2 has a previously unappreciated role in the production of high-affinity antibodies.
[Mh] Termos MeSH primário: Linfócitos B/imunologia
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo
Citidina Desaminase/metabolismo
Conversão Gênica
Genes de Imunoglobulinas
Hipermutação Somática de Imunoglobulina
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Animais
Linfócitos B/metabolismo
Diferenciação Celular
Galinhas
Regulação da Expressão Gênica
Switching de Imunoglobulina
Fatores de Transcrição/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Basic-Leucine Zipper Transcription Factors); 0 (Transcription Factors); EC 3.5.4.- (AICDA (activation-induced cytidine deaminase)); EC 3.5.4.5 (Cytidine Deaminase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170317
[St] Status:MEDLINE
[do] DOI:10.1002/eji.201646895



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BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde