RESUMO
The current academic and business landscape does not provide a clear path for doctoral trainees graduating. Moreover, the fundamental need of the hour is diversification of the workforce where PhD graduates need to be trained to do more beyond basic scientific research. One of the possible paths that is now becoming popular as science enters its translational phase is research commercialization and technology transfer. This short article provides an comprehensive overview of the technology transfer field and possible paths trainees can take to position themselves as a successful technology transfer professional.
Assuntos
Escolha da Profissão , Mobilidade Ocupacional , Comércio , Pesquisadores , Transferência de Tecnologia , Humanos , Descrição de Cargo , Aprendizagem , Masculino , Marketing , Negociação , Rede Social , Habilidades SociaisRESUMO
Recently, many advancements in genome-wide chromatin topology and nuclear architecture have unveiled the complex and hidden world of the nucleus, where chromatin is organized into discrete neighbourhoods with coordinated gene expression. This includes the active and inactive X chromosomes. Using X chromosome inactivation as a working model, we utilized publicly available datasets together with a literature review to gain insight into topologically associated domains, lamin-associated domains, nucleolar-associating domains, scaffold/matrix attachment regions, and nucleoporin-associated chromatin and their role in regulating monoallelic expression. Furthermore, we comprehensively review for the first time the role of chromatin topology and nuclear architecture in the regulation of genomic imprinting. We propose that chromatin topology and nuclear architecture are important regulatory mechanisms for directing gene expression within imprinted domains. Furthermore, we predict that dynamic changes in chromatin topology and nuclear architecture play roles in tissue-specific imprint domain regulation during early development and differentiation.
Assuntos
Núcleo Celular/química , Cromatina/química , Impressão Genômica , Inativação do Cromossomo X , Animais , Diferenciação Celular , Núcleo Celular/metabolismo , Cromatina/metabolismo , Humanos , Camundongos , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , RNA Longo não Codificante/química , RNA Longo não Codificante/metabolismoRESUMO
Genomic imprinting is a phenomenon that restricts transcription to predominantly one parental allele. How this transcriptional duality is regulated is poorly understood. Here we perform an RNA interference screen for epigenetic factors involved in paternal allelic silencing at the Kcnq1ot1 imprinted domain in mouse extraembryonic endoderm stem cells. Multiple factors are identified, including nucleoporin 107 (NUP107). To determine NUP107's role and specificity in Kcnq1ot1 imprinted domain regulation, we deplete Nup107, as well as Nup62, Nup98/96 and Nup153. Nup107, Nup62 and Nup153, but not Nup98/96 depletion, reduce Kcnq1ot1 noncoding RNA volume, displace the Kcnq1ot1 domain from the nuclear periphery, reactivate a subset of normally silent paternal alleles in the domain, alter histone modifications with concomitant changes in KMT2A, EZH2 and EHMT2 occupancy, as well as reduce cohesin interactions at the Kcnq1ot1 imprinting control region. Our results establish an important role for specific nucleoporins in mediating Kcnq1ot1 imprinted domain regulation.
Assuntos
Endoderma/metabolismo , Impressão Genômica , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , RNA Longo não Codificante/genética , Células-Tronco/metabolismo , Animais , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Cruzamentos Genéticos , Embrião de Mamíferos , Endoderma/citologia , Endoderma/crescimento & desenvolvimento , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/genética , Histonas/metabolismo , Masculino , Camundongos , Proteína de Leucina Linfoide-Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Longo não Codificante/metabolismo , Células-Tronco/citologia , CoesinasRESUMO
Microinjection has a long and distinguished history in Xenopus and has been used to introduce a surprisingly diverse array of agents into embryos by both intra- and intercellular means. In addition to nuclei, investigators have variously injected peptides, antibodies, biologically active chemicals, lineage markers, mRNA, DNA, morpholinos, and enzymes. While enumerating many of the different microinjection approaches that can be taken, we will focus upon the mechanical operations and options available to introduce mRNA, DNA, and morpholinos intracellularly into early stage embryos for the study of neurogenesis.