Understanding the words of chromatin regulation

Abstract

Recent studies indicate that chromatin regulatory complexes produce biological specificity in the way that letters produce meanings by combinations into words. Combinatorial assembly of chromatin regulatory complexes may be critical for maximizing the information content provided by arrays of histone modifications.

Figure 1. Combinatorial Assembly of Chromatin Regulatory Complexes

Shown is the predicted combinatorial diversity for the mammalian chromatin regulatory complexes: BAF (mSWI/SNF), NuRD, ISWI, and Polycomb (the number of possible combinations is shown in parentheses in red). (Top) Three examples of BAF complexes illustrate respelling of the chromatin remodeling word by switching subunit composition. The subunits are depicted as interlocking pieces in which a similar shape of the subunit denotes homology and thereby a specific position in the complex. Subunits shown in dashed outline are inconstant components of the complexes. The positions of the proteins in the complexes are arbitrary 2D projections, except for actin and BAF53, which contact the catalytic domain of Brg (Zhao et al., 1998). The depicted area of each subunit is roughly proportional to its mass.

Figure 2. Biological Specificity by Combinatorial Assembly

Alternative, but not mutually exclusive, models for generating biological specificity by combinatorial assembly of ATP-dependent chromatin remodeling complexes. (A) Composite surface model in which transcription factors (TF) bind at interfaces of the subunits. (B) Conformational model in which the arrangement of histone modification recognition domains and DNA-binding domains within the complex leads to recognition of specific loci. Brg, BAF155, BAF170, BAF45, and BAF57 have either DNA-binding domains or domains that bind to modified histones and hence could target the complex to specific developmental loci independent of, or in cooperation with, transcription factors. (Not all of the domains are shown, but an exhaustive list appears in Table 1.) BAF-mediated looping of chromatin (suggested by in vitro studies) illustrates the size of the BAF complex and its potential multivalent interactions with chromatin.