Chromatin Remodeling

Eukaryotic DNA is tightly packaged into repeated structures known as nucleosomes. Individual nucleosomes consist of a nucleosome core with 146 (or 147) base pairs of double-helix DNA wrapped around it over 1.65 turns to create a superhelix. Nucleosome cores are composed of histone octamers, that consist of a H3(2):H4(2) tetramer and two dimers of H2A and H2B. Nucleosomes reduce the binding of a variety of DNA regulatory proteins including transcription, DNA repair and recombination machinery. For example, the relative binding of specificity protein 1 (SP1) and TFIIIA to nucleosomal DNA versus free DNA is one order of magnitude lower. Derepression of these processes requires chromatin remodeling to expose segments of DNA that can interact with gene expression or DNA repair machinery.

Chromatin remodeling involves the effective shifting of nucleosome cores along the length of the DNA molecule, a process known as “nucleosome sliding”. Recent studies suggest that this shift may involve the actual disassembly and reassembly of the nucleosome core.

Chromatin remodeling is accomplished, at least in part, by ATPase containing complexes, referred to as the SWI/SNF family. Chromatin remodeling complexes are grouped into four subfamilies based upon their associated ATPase. The four ATPases associated with chromatin remodeling complexes are SWI2/SNF2 (mammalian Brm (SNF2α) and Brg1 (SNF2β)); imitation switch (ISWI); Mi-2 (CHD1) and INO80.

Individual ATPase family chromatin remodeling complexes provide a level of regulatory control and specificity to the general process of chromatin remodeling. The SWI/SNF complex in Saccharomyces cerevisiae is composed of at least 11 polypeptides. The ISWI complexes are divided into the nucleosome remodeling factor (NURF), chromatin accessibility complex (CHRAC), and ATP-dependent chromatin and remodeling factor (ACF) complexes. NURF is composed of ISWI and three additional subunits, NURF301, NURF55 and NURF38. The SWI/SNF family members differentiate at the level of DNA sequence and gene structure.

References:

1. Lorch, Y. et. al. (2006) Chromatin remodeling by nucleosome disassembly in vitro. Proc. Natl. Acad. Sci. USA. 103, 3090-3093.
   
   
2. Ooi, L. et. al. (2006) BRG1 Chromatin Remodeling Activity Is Required for Efficient Chromatin Binding by Repressor Element 1-silencing Transcription Factor (REST) and Facilitates REST-mediated Repression. J. Biol. Chem. 281, 38974-38980.
   
   
3. Villagra, A. et. al. (2006) Chromatin remodeling and transcriptional activity of the bone-specific osteocalcin gene require CCAAT/enhancer-binding protein beta-dependent recruitment of SWI/SNF activity. J. Biol. Chem. 281, 22695-22706.
   
   
4. Xu, Z. et. al. (2006) Recruitment of the SWI/SNF protein Brg1 by a multiprotein complex effects transcriptional repression in murine erythroid progenitors. Biochem. J. 399, 297-304.