Fig. 5.

Sox2 binds to both pseudo and consensus motifs in the LIN28B nucleosome through DNA allostery. (A) Distribution of the DNA positioning u that describes the sliding of DNA in LIN28B nucleosome; $u$ is defined by the index of the phosphate that is the closest to Lys64 in the histone H3 (the red ball in Inset). Error bars are based on bootstrapping (SI Appendix, Supplementary Methods). (B) Structure of the LIN28B nucleosome at the most populated sliding position $u=104$. The consensus motif (“AACAATA” at DNA index 59 to 65, cyan) has its minor groove facing “inward,” whereas a pseudo motif (“GATTGTG” at 144 to 150, yellow) has its minor groove exposed. (C) Binding probability of Sox2 on the LIN28B nucleosome starting from the $u=104$ state (Lower). Binding energy score (represented by blue intensity) and the exposure score (${\varphi }_{minor}$, gray for 0 and white for 1) (Upper and Middle). The positions of the consensus and the pseudo motifs in B are indicated by the solid and the blank triangles. (D) A representative time series of the Sox2 binding position ($b_{Sox2}$, Lower) and the sliding of nucleosomal DNA ($u$, Middle) in the LIN28B nucleosome. Two DNA structures are shown to illustrate the rotational position of the consensus motif at $u=104$ and $u=101$, respectively (Upper). (E) A representative structure of Sox2 binding on the pseudo motif. We show a fraction of end DNA from the superimposed free nucleosome (white) to compare with the sharply bent DNA caused by Sox2 binding. (F) Distribution of the sliding coordinate $u$ in the simulations that have one Sox2 binding on the pseudo motif as the initial structure. (G) DNA contact probability of the second Sox2, analyzed from the simulations in which one Sox2 was bound to the pseudo motif in the initial structure. (H) A representative structure of the two Sox2−LIN28B nucleosome bindings, with the second Sox2 binding on the consensus motif.