Regulation and Impact of Chromatin Decondensation in Mammalian Cells

50 years ago Vincent Allfrey and colleagues discovered that lymphocyte activation promotes histone acetylation and gene expression. Recent studies clarified that G₀ B cells proportionally amplify their transcriptome upon stimulation by a mechanism that involves Myc and TFIIH. We now show that B cell chromatin undergoes massive decondensation by the amplification of histone acetylation, methylation, and nucleosome remodeling. Super-resolution microscopy revealed that histone acetylation triggers rapid spreading of chromatin nanodomains from the periphery to the entire nucleus. Furthermore, nanodomains decompact into single nucleosome fibers by a process that requires Myc and ATP production. Using single molecule tracking, we show that chromatin decompaction increases the dynamics of transcription factor binding. Architecturally, B cell activation mediates a marked shift from long-range to short-range interactions and the formation of loops and contact domains that facilitate interaction between cognate regulatory elements. The data thus reveal the epigenetic and topological features that support transcriptome amplification, and help explain the primed nature of B cells.