Chromatin remodeling: a marriage between two families? Kerri J. Pollard and Craig L. Peterson* Summary The compaction of the eukaryotic genome into a highly folded chromatin structure necessitates cellular mechanisms for allowing access of regulatory proteins to the DNA template. Recent advances in the fields of gene silencing, transcription, recombination, and DNA repair have led to the identification of two distinct families of chromatin remodeling enzymes—nuclear histone acetyltransferases and multi- subunit complexes that harbor a SWI2/SNF2 ATPase family member. This paper reviews the current notion of how these enzymes function in remodeling chroma- tin; we then discuss some tantalizing lines of evidence that lead to the hypothesis that members of both families may actually function in concert to facilitate cellular processes in the context of chromatin. BioEssays 20:771–780, 1998.  1998 John Wiley & Sons, Inc. Introduction A typical eukaryotic cell contains over three linear feet of DNA that must be extensively folded so that it can squeeze into a nucleus of about 20 μm in diameter. The primary level of compaction of eukaryotic DNA is the formation of linear arrays of nucleosome core particles. A nucleosome core consists of about 146 base pairs (bp) of DNA wrapped 1.75 times around a complex of eight histone proteins—two each of H2A, H2B, H3, and H4. This initial arrangement, commonly referred to as a ‘‘beads on a string’’ structure, is then further folded into a chromatin fiber of at least 30 nM in diameter. Cytological studies (1,2) indicate that 100- to 200-nM fibers predominate the structure of bulk chromatin in an interphase nucleus, a cell cycle period in which the genome must be accessible to the transcription, replication, repair, and recom- bination machinery. The organization of DNA into chromatin necessitates mechanisms to rapidly and reversibly unfold or de-compact specific loci so that DNA sequences are accessible to enzymes that must ‘‘read’’ the cell’s genetic material. Two broad families of enzymes may have evolved to contend with this difficult task. The SWI2/SNF2 family of DNA-stimulated ATPases appears to define a large number of enzymes that play roles in diverse cellular processes such as transcription, repair, and recombination (reviewed in ref. 3). Several mem- bers of the SWI2/SNF2 family are components of multi- subunit complexes that can either disrupt the structure of nucleosome core particles or influence the mobility and spacing of nucleosome arrays. (4–8) Genetic studies in yeast indicate that additional SWI2/SNF2 family members may also function by contending with chromatin (9) (reviewed in ref. 10). Studies of transcriptional activation in yeast and of several mammalian coactivators for nuclear hormone receptors have led to the identification of an additional ‘‘family’’ of proteins, the nuclear histone acetyltransferases. The covalent modifica- tion of histones by acetyltransferases may cause subtle changes in nucleosome core structure, disrupt or promote the interaction of nonhistone proteins with the chromatin fiber, or control the folding of nucleosome arrays (reviewed in refs. 11, 12). Genetic and biochemical evidence is now accumulating which suggests that these two families of chromatin remodel- ing enzymes may work together, rather than independently, to contend with chromatin-mediated repression of cellular pro- cesses. Program in Molecular Medicine and Department of Biochemistry and Molecular Biology, University of Massachusetts Medical Center, Worcester, Massachusetts. *Correspondence to: Craig L. Peterson, Program in Molecular Medi- cine and Department of Biochemistry and Molecular Biology, Univer- sity of Massachusetts Medical Center, 373 Plantation Street, Worces- ter, MA 01605; E-mail: craig.peterson@ummed.edu Hypothesis BioEssays 20:771–780,  1998 John Wiley & Sons, Inc. BioEssays 20.9 771