Chromatin Remodeling Proteins

Division Of Basic Sciences - Nci

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Abstract

We have characterized CReMM, a new member of the CHD family of chromatin remodeling proteins. CReMM is rearranged in a large fraction of osteosarcomas, implicating the disruption of this new protein in an important human disease. This protein was isolated by immunocloning from marrow stromal cells, and contains motifs for interaction with steroid receptors. Molecular clones of the CReMM protein have been characterized. A large fragment representing 85% of the protein has been expressed in baculovirus and purified from infected cells. This protein has been shown to have DNA dependent ATPase activity, and to carry out nucleosome remodeling by two separate assays, nucleosome sliding, and nuclease resolved nucleosome reorganzation. Thus, the CReMM protein is a functional member of the CHD remodeling family. We have developed dominant negative forms of the INO80 and Snf2h human chromatin remodeling proteins, and have characterized the biochemical activity of these complexes. We are studying the potential role of these remodeling systems in the action of nuclear receptors at specific sites of remodeling genome wide.