Epigenetic regulation of DNA damage and repair

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5-hydroxymethylcytosine (5hmC) is a DNA base created during active DNA demethylation by the recently discovered TET enzymes. 5hmC has essential roles in gene expression and differentiation. We found that 5hmC also localizes to sites of DNA damage and repair. 5hmC accumulates at damage foci and colocalizes with major DNA damage response proteins 53BP1 and gH2AX, revealing 5hmC as an epigenetic marker of DNA damage. We are trying to understand the role of 5hmC in maintaining genome integrity.


Epigenetic regulation of stem cell differentiation 

A second effort of our group focuses on how the genome is regulated through covalent modification of histones or DNA itself. 

While genome-wide biochemical techniques to study chromatin modification have revealed high-resolution maps of DNA and histone modifications. However, these studies do not show the three-dimensional distribution of these modifications in the nucleus, nor can they show relevant variation between cells. Using various mammalian cultured cell lines, including embryonic stem (ES) cells of human and mouse, combined with high-resolution three-dimensional fluorescence imaging, we are investigating the dynamic changes of DNA and histone modifications that occur in processes such as pluripotency loss, differentiation, and the DNA damage response.