C.R. Clapier et al. Figure 1 Sequence alignment of histones. Alignment of histones from Drosophila (Dm), Xenopus (Xl), chicken (Gg), mouse (Mm), human (Hs), and yeast (Sc). Drosophila H2A, H2B, H3, H4 sequences correspond to accession codes NP_724343, NP_724342, NP_724345, NP_724344, respectively. Only residues that differ from the Drosophila sequence are shown. Amino acid substitutions that differentiate the Drosophila and Xenopus histone core regions are highlighted in yellow and cyan; those in ordered tail residues are highlighted in pink. Unstructured residues are indicated in lower case. Amino acid substitutions in the histone cores Twelve amino acid substitutions differentiate Drosoph- ila from Xenopus within the histone core regions. Five substitutions are highly conservative replacements involv- ing solvent-exposed, small (Gly, Ala, or Ser) residues which do not interact with other residues nor with the DNA (Fig. 1, highlighted in yellow). Three of these five substitutions [Gly98 ? Ser in H2A; Gly72 ? Ala in H2B; and Ala102 ? Gly in H3 (written as Xenopus ? Figure 2 Figure 3 4 PROTEINS Structural differences within the H2A and H2B histone tails between Dm-NCP147 and Xla-NCP147. (a) Dm-NCP viewed along the superhelix showing the location of the N-terminal tail of H2A. (b) The N-terminal histone tail of H2A0, showing close-up of boxed region in a. Side chains from Drosophila are in light gray; from Xenopus in dark Grey. Hydrogen bonds unique to Drosophila are in black; those unique to Xenopus are in red. Residue substitutions are labelled in the direction from Xenopus to Drosophila. DNA bases are shown as sticks, except for Thy45. The view is slightly rotated relative to that in a. (c) Edge view of the NCP showing location of the N- terminal tail of H2B. (d) Histone tail of H2B0 showing close-up view of boxed region in c. Base atoms is shown for Thy50 and Cyt-49. Structural differences in the H2A-H2B dimer between Dm-NCP147 and Xla-NCP147. (a) Overview of structured residues in the hydrophobic core of the H2A-H2B dimer that diverge between Xenopus and Drosophila. View is approximately along the pseudodyad. (b) Compensatory changes within the hydrophobic core of H2A. Residue substitutions are labeled in the direction from Xenopus to Drosophila. (c) Compensatory changes involving two residues in the H2A-H2B dimer interface. The hydrogen bond missing from the Dm structure is in red. (d) Compensatory changes involving three residues in the H2A-H2B dimer interface.