Inter-nucleosomal communication between histone modifications for nucleosome phasing
Fig 4
Association of the H4K20me1-H2A.Z interaction with nucleosome profile patterns around TSS.
(a) Four clusters of the nucleosome profiles in -2000 ~ +2000 bp regions surrounding TSS. The H4K20me1-H2A.Z interaction was obtained in Cluster 1, 3 and 4. (b) Length, depth and size of nucleosome free regions, and gene transcription levels for each of the four TSS clusters. The mean and standard error of the mean (SEM) are shown. One-way ANOVA was used for overall comparison, and TukeyHSD test was used to calculate the p-values between Cluster 2 and other clusters. (c) Pipeline for calculating Nucleosome Phasing Index. Nucleosome Phasing Index was quantified based on the Jensen-Shannon divergence distance (JSD) between the binary template vector and the binary-converted nucleosome-signal vector of each TSS (see Methods for details). (d) Phasing Index for each of the four TSS clusters. Statistical tests were same as (b). (e-g) Cross-group linear regression for H4K20me1-H2A.Z anti-correlation versus the NFR length (e), depth (f), and size (length × depth) (g) downstream of TSSs, respectively. Adjusted R2 and p-values are labeled on the panels. (h-j) Same as (e-g), but for the H2A.Z-H4K20me1 anti-correlation at TSS upstream. (k) Cross-group linear regression for H4K20me1-H2A.Z anti-correlation versus nucleosome Phasing Index. (l) Mechanistic model of the H2A.Z-H4K20me1 inter-nucleosome interaction. For lowly expressed genes, neither H2A.Z or H4K20me1 is present (Scenario 1), where H2A and H4K20 from neighboring nucleosome can weakly interact to form a weak interaction between nucleosomes and phasing around TSS through the weak acidic patch of H2A; If there exist H4K20me1 (Scenario 2), it would disrupt inter-nucleosome interaction, cause loss of phasing, and expose DNA to spurious transcription, which is an unfavorable situation. For highly expressed genes, the presence of both H2A.Z and H4K20me1 (Scenario 3) will make a flexible and controllable strong interaction between H4K20me1 of the neighboring nucleosome through the strong acidic patch of H2A.Z; Alternatively, if H4K20 is not methylated (Scenario 4), the interaction is too strong to be regulated and has a propensity to form condensed chromatin structure. The strong extended H2A.Z acidic patch is represented by a lock.