Abstract
Mammals face and overcome an onslaught of endogenous and exogenous challenges in order to survive. Typical immune cells and barrier cells, such as epithelia, must respond rapidly and effectively to encountered pathogens and aberrant cells to prevent invasion and eliminate pathogenic species before they become overgrown and cause harm. On the other hand, inappropriate initiation and failed termination of immune cell effector function in the absence of pathogens or aberrant tissue gives rise to a number of chronic, auto-immune, and neoplastic diseases. Therefore, the fine control of immune effector functions to provide for a rapid, robust response to challenge is essential. Importantly, immune cells are heterogeneous due to various factors relating to cytokine exposure and cell-cell interaction. For instance, tissue-resident macrophages and T cells are phenotypically, transcriptionally, and functionally distinct from their circulating counterparts. Indeed, even the same cell types in the same environment show distinct transcription patterns at the single cell level due to cellular noise, despite being robust in concert. Additionally, immune cells must remain quiescent in a naive state to avoid autoimmunity or chronic inflammatory states but must respond robustly upon activation regardless of their microenvironment or cellular noise. In recent years, accruing evidence from next-generation sequencing, chromatin capture techniques, and high-resolution imaging has shown that local- and long-range genome architecture plays an important role in coordinating rapid and robust transcriptional responses. Here, we discuss the local- and long-range genome architecture of immune cells and the resultant changes upon pathogen or antigen exposure. Furthermore, we argue that genome structures contribute functionally to rapid and robust responses under noisy and distinct cellular environments and propose a model to explain this phenomenon.
Highlights
Survival requires that organisms withstand the constant assault of external and internal threats
This shows clearly that chromatin structure does parallel the needs of immune regulation, and, provides another avenue of regulatory leverage which could satisfy the needs of the immune response
We reviewed that immune cells make rapid response possible by preformed “ready-to-respond” and it’s a risk of autoimmune diseases
Summary
Survival requires that organisms withstand the constant assault of external and internal threats. P-TEFb is recruited to the PIC and, in turn, phosphorylates serine residues at the second and fifth amino acid from N-terminal; phosphorylation dissociates NELF allowing elongation to begin and the full-length transcript is subsequently synthesized [3, 4] These are the minimum requirements for transcription; without additional potentiating factors baseline expression remains low. Accruing evidence demonstrates that features of chromatin structure at a range of scales are central to effective immune regulation This includes creating permissive environments for rapid gene induction and modifying chromatin structure to encode epigenetic memory and prompt cell activation. An interface exists between predictable processes and random events which govern chromatin structure creating a potential space for heterogeneity and inducibility This shows clearly that chromatin structure does parallel the needs of immune regulation, and, provides another avenue of regulatory leverage which could satisfy the needs of the immune response. Second, how rapid and versatile immune responses facilitated by chromatin structure underlie immunemediated conditions, like auto-immunity
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