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A01 - Alexander Brehm:

Epigenome regulation by ATP-dependent nucleosome remodelers

The ATP-dependent nucleosome remodeler CHD4/Mi-2 plays pivotal roles in normal differentiation and malignancy. In the past funding period we have unraveled molecular mechanisms that direct CHD4/dMi-2 to its sites of action on chromatin. We will build on these insights to uncover the effects of CHD4/Mi-2 mutations identified in cancer and neurodevelopmental disorders on CHD4/Mi-2 remodeling activity and the epigenome. In addition, we will investigate different approaches to modulate CHD4/Mi-2 activity by small molecules and peptides with the long term goal to ameliorate the consequences of defective nucleosome remodeling in disease.

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