UHRF1 SRA domain bound with hemi-methylated CpG

SRA domain of UHRF1 binds hemimethylated CpG and flips  5-methylcytosine out of the DNA helix, whereas its tandom tudor domain and PHD domain bind the tail of histone H3 in a highly methylation sensitive manner." title="UHRF1-Enhancer-Binding-Proteins-CpG-Islands-DNA-Methylation-Epigenesis-Nuclear-Proteins-hemimethylated-cytosine-binding-protein

SRA domain of UHRF1 binds hemimethylated CpG and flips 5-methylcytosine out of the DNA helix, whereas its tandom tudor domain and PHD domain bind the tail of histone H3 in a highly methylation sensitive manner.\

 

Cytosine methylation in DNA is a major epigenetic signal, and plays a central role in propagating chromatin status during cell division. However the mechanistic links between DNA methylation and histone methylation are poorly understood. A multi-domain protein UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is required for DNA CpG maintenance methylation at replication forks, and mouse UHRF1-null cells show enhanced susceptibility to DNA replication arrest and DNA damaging agents. Recent data demonstrated that the SET and RING associated (SRA) domain of UHRF1 binds hemimethylated CpG and flips 5-methylcytosine out of the DNA helix, whereas its tandom tudor domain and PHD domain bind the tail of histone H3 in a highly methylation sensitive manner. We hypothesize that UHRF1 brings the two components (histones and DNA) carrying appropriate markers (on the tails of H3 and hemimethylated CpG sites) ready to be assembled into a nucleosome after replication.

 
Enzimas que reconocen las marcas epigenéticas.

La metilación de la cistosinas del ADN es una de las principales marcas epigenéticas, y juega un papel central en la propagación del estado de la cromatina en la división celular. En la imagen se ve la enzima UHRF1 que reconce el ADN marcado hemimetilado (marcado en una de sus hebras) y como se une a estas marcas de citosinas metiladas. Tras unirse es capaz de romper los puntes de hidrógeno que establece la base metilada con su par y sacarla del eje de la doble hélice. Queda así, anclada preparada para interaccionar con una metilasa de ADN que copie el patrón de marcas en la hebra complementaria.

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