RESUMO
The interaction of microbiota with its host has the ability to alter the cellular functions of both, through several mechanisms. Recent work, from many laboratories including our own, has shown that epigenetic mechanisms play an important role in the alteration of these cellular functions. Epigenetics broadly refers to change in the phenotype without a corresponding change in the DNA sequence. This change is usually brought by epigenetic modifications of the DNA itself, the histone proteins associated with the DNA in the chromatin, non-coding RNA or the modifications of the transcribed RNA. These modifications, also known as epigenetic code, do not change the DNA sequence but alter the expression level of specific genes. Microorganisms seem to have learned how to modify the host epigenetic code and modulate the host transcriptome in their favour. In this review, we explore the literature that describes the epigenetic interaction of bacteria, fungi and viruses, with their mammalian hosts.
Assuntos
Bactérias/patogenicidade , Fenômenos Fisiológicos Bacterianos , Epigênese Genética , Mamíferos/genética , Vírus/patogenicidade , Animais , Metilação de DNA , Fungos/patogenicidade , Fungos/fisiologia , Histonas/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Mamíferos/microbiologia , Mamíferos/virologia , RNA/metabolismoRESUMO
Non-mendelian inheritance refers to the group of phenomena and observations related to the inheritance of genetic information that cannot be merely explained by Mendel's laws of inheritance. Phenomenon including Genomic imprinting, X-chromosome Inactivation, Paramutations are some of the best studied examples of non-mendelian inheritance. Genomic imprinting is a process that reversibly marks one of the two homologous loci, chromosome or chromosomal sets during development, resulting in functional non-equivalence of gene expression. Genomic imprinting is known to occur in a few insect species, plants, and placental mammals. Over the years, studies on imprinted genes have contributed immensely to highlighting the role of epigenetic modifications and the epigenetic circuitry during gene expression and development. In this review, we discuss the phenomenon of genomic imprinting in mammals and the role it plays especially during fetoplacental growth and early development.
Assuntos
Metilação de DNA/genética , Impressão Genômica/genética , Código das Histonas/genética , Inativação do Cromossomo X/genética , Animais , Evolução Biológica , Feminino , Humanos , Mamíferos/genética , Placenta/metabolismo , GravidezRESUMO
L-Asparaginase (3.5.1.1) being antineoplastic in nature are used in the treatment of acute lymphoblastic leukemia (ALL). However glutaminase activity is the cause of various side effects when used as a drug against acute lymphoblastic leukemia (ALL). Therefore, there is a need of a novel L-asparaginase (L-ASNase) with low or no glutaminase activity. Such a property has been observed with L-ASNase from B. licheniformis (BliA). The enzyme being glutaminase free in nature paved the way for its improvement to achieve properties similar to or near to the commercially available L-ASNases. Rational enzyme engineering approach resulted in four mutants: G238N, E232A, D103V and Q112H. Among these the mutant enzyme, D103V, had a specific activity of 597.7IU/mg, which is higher than native (rBliA) (407.65IU/mg). Moreover, when the optimum temperature and in vitro half life were studied and compared with native BliA, D103V mutant BliA was better, showing tolerance to higher temperatures and a 3 fold higher half life. Kinetic studies revealed that the mutant D103V L-ASNase has increased substrate affinity, with Km value of 0.42mM and Vmax of 2778.9µmolmin(-1).
