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Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
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Persistencia evolutiva de la metilación del ADN durante millones de años después de la pérdida antigua de una De Novo

Sandra Catania1, Phillip A Dumesic1, Harold Pimentel2

  • 1Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.

Cell
|January 21, 2020
PubMed
Resumen

La metilación del ADN en Cryptococcus neoformans persiste a través de un mecanismo de mantenimiento, análogo a la evolución darwiniana. Esta herencia epigenética ha continuado durante más de 50 millones de años a pesar de la pérdida de una metilasa de novo.

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Cryptococcus neoformans, también conocido como criptococoMetilación del ADNCromatina y sus derivadosMemoria epigenéticaLa epigenéticaLa evoluciónElementos transponibles

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Área de la Ciencia:

  • La epigenética
  • Biología molecular
  • Genética de la levadura

Sus antecedentes:

  • La metilación del ADN es una modificación epigenética crítica involucrada en varios procesos biológicos.
  • En Cryptococcus neoformans, la metilación CG se observa en regiones ricas en transposones y está mediada por la ADN metiltransferasa Dnmt5.
  • La metilación del ADN metazoario se basa en las metilasas de mantenimiento como Dnmt1.

Objetivo del estudio:

  • Para investigar el mecanismo de mantenimiento de la metilación del ADN en Cryptococcus neoformans.
  • Para entender cómo se propagan los patrones de metilación en escalas de tiempo evolutivas.
  • Para explorar la historia evolutiva de las metiltransferasas de ADN en esta levadura.

Principales métodos:

  • Ensayos bioquímicos in vitro e in vivo para determinar la especificidad de Dnmt5.
  • Análisis filogenético para rastrear la historia evolutiva de las metiltransferasas de ADN.
  • Estudios experimentales relacionados con la replicación de patrones de metilación, pérdida y ganancia de eventos en C. neoformans.
  • Estudios genómicos comparativos.

Principales resultados:

  • Dnmt5 exhibe una alta especificidad de tipo de mantenimiento, utilizando cofactores similares al metazoo Dnmt1.
  • El análisis filogenético indica la pérdida de una metilasa de novo (DnmtX) en el linaje ancestral de C. neoformans hace entre 50 y 150 millones de años.
  • Los patrones de metilación se replican eficientemente durante la división celular, con cambios estocásticos raros.
  • La selección natural actúa sobre los patrones de metilación, influyendo en su persistencia.

Conclusiones:

  • Cryptococcus neoformans mantiene la metilación del ADN a través de un mecanismo de replicación eficiente, basado principalmente en Dnmt5.
  • La propagación a largo plazo de los patrones de metilación (> 50 millones de años) en C. neoformans está impulsada por la fidelidad de la replicación, los eventos estocásticos raros y la selección natural.
  • Este proceso de herencia epigenética es análogo a la evolución darwiniana, destacando una estrategia evolutiva única para mantener la información epigenética.