The authors show that genes can be separated into distinct low or high expression abundance groups. Histone marks reveal that this switch-like transition from low to high expression goes hand-in-hand with a change in chromatin status.

Many proteins expressed in Escherichia coli cells form inclusion bodies that are neither refoldable nor soluble in buffers. Very surprisingly, we recently discovered that all 11 buffer-insoluble protein fragments/domains we have, with a great diversity of cellular function, location, and molecular size, could be easily solubilized in salt-free water. The circular dichroism (CD) and NMR characterization led to classification of these proteins into three groups: group 1, with no secondary structure by CD and with narrowly-dispersed but sharp (1)H-(15)N heteronuclear single quantum correlation (HSQC) peaks; group 2, with secondary structure by CD but with HSQC peaks broadened and, consequently, only a small set of peaks detectable; and group 3, with secondary structure by CD and also well-separated HSQC peaks. Intriguingly, we failed to find any protein with a tight tertiary packing. Therefore, we propose that buffer-insoluble proteins may lack intrinsic ability to reach or/and to maintain a well-packed conformation, and thus are trapped in partially-folded states with many hydrophobic side chains exposed to the bulk solvent. As such, a very low ionic strength is sufficient to screen out intrinsic repulsive interactions and, consequently, allow the hydrophobic clustering/aggregation to occur. Marvelously enough, it appears that in pure water, proteins have the potential to manifest their full spectrum of structural states by utilizing intrinsic repulsive interactions to suppress the attractive hydrophobic clustering. Our discovery not only gives a novel insight into the properties of insoluble proteins, but also sheds the first light that we know of on previously unknown regimes associated with proteins.

During early differentiation of T helper cells, stochastic cytokine expression triggers the co-expression of antagonistic transcription factors at high levels, buffered by the interplay between extracellular and intracellular signaling components.