Defining the Transcriptional Ecosystem

Control of Cell Identity by the Nuclear Receptor HNF4 in Organ Pathophysiology

“…Temporary shutdown of cell identity, when defined as a transient decrease in the expression of genes involved in tissue-specific functions such as HNF4 factors, may be beneficial in situations of acute injury to permit the cells to reallocate their transcriptional resources. Indeed, competition for transcriptional supplies has been proposed to rule transient transcriptional adaptations to environmental disturbances in a model referred to as transcriptional ecosystem [ 135 ]. Hence, the transient decrease in the expression HNF4 and other TFs involved in cell identity upon acute injury may be necessary to allow the increased expression of stress/injury handling genes [ 69 ], as well as genes involved in DNA synthesis and cell proliferation enabling repopulation of the damaged liver [ 68 , 125 ] ( Figure 2 ).…”

Chromatin domains in space and their functional implications

“…In addition, we also speculate that transcriptional regulators are involved in forming these chromatin contacts (Figure 1a) (see discussion in the next section). Together, the cooperative interactions among multiple transcribed loci form a spatial domain of "transcriptional ecosystem equilibrium" in the nucleus that fosters co-expression patterns [57]. Such physical interactions among active chromatin could be a mechanism underlying coexpression of metabolic genes residing close to each other (i.e., members belonging to a gene cluster annotated in the linear genome) [58,59].…”

“…This study also gives us a hint that the interactions between RNA-binding proteins and chromatin in plants might have been unsuspected.As discussed earlier, there is a correlation between chromatin domains and their local epigenetic signatures. In addition, to assess the transcriptional regulation of a given gene, it is essential to identify all the direct and indirect interacting-factors of the gene, i.e., the other genomic regions, RNA, and proteins[57]. Moreover, the supra-moleculararrangements created by LLPS also seem to play a role in protein regulation via their retention as demonstrated for the DNA methyltransferase DNMT1, retained in the nucleolus during acidosis in human cells (Audas et al 2012).…”

Dynamic regulation of promoter-proximal RNA polymerase II pausing

“…同的转录相关因子是如何招募包括RNA Pol II在内的 转录机器, 并平衡启动子近端暂停和延伸过程 [46,105] . 转 录凝聚物的高度动态性确保了高浓度延伸因子的聚集, 催化反应的高效率, 转录延伸的快速发生, 这样才使得 转录过程能够响应各发育阶段不同的信号刺激 [106,107] .…”