Robust and efficient gene regulation through localized nuclear microenvironments

Abstract

Developmental enhancers drive gene expression in specific cell types during animal development. They integrate signals from many different sources mediated through the binding of transcription factors, producing specific responses in gene expression. Transcription factors often bind low-affinity sequences for only short durations. How brief, low-affinity interactions drive efficient transcription and robust gene expression is a central question in developmental biology. Localized high concentrations of transcription factors have been suggested as a possible mechanism by which to use these enhancer sites effectively. Here, we discuss the evidence for such transcriptional microenvironments, mechanisms for their formation and the biological consequences of such sub-nuclear compartmentalization for developmental decisions and evolution.

Developmental phenomics suggests that H3K4 monomethylation catalyzed by Trr functions as a phenotypic capacitor

“…Thus, this focus on phenotypic changes across developmental scales provided a mechanistic link between H3K4me1 and its role in fostering developmental robustness through transcriptional microenvironments (Figure 4). Even though they appear to be a central feature of gene expression, the regulatory mechanisms underlying these microenvironments and their resulting physiological implications are just starting to be explored 23 . DNA accessibility is usually considered a key element in the clustering of transcription factors and polymerases in transcriptional hubs 37 ; however, evidence for a histone mark playing a role in the organization or maintenance of nuclear microenvironments had not been reported before.…”

Wheat Breeding, Transcription Factories, and Genetic Interactions: New Perspectives

“…Because loops and loop complexes are associated with RNA Polymerase ll, it is concluded that they form “transcription factories” (TFs) ( Figure 2D ; Schoenfelder et al, 2009 ; Sutherland and Bickmore, 2009 ; Concia et al, 2020 ). These factories are assumed to include many other molecules, such as coactivators, chromatin remodelers, transcription factors, histone modification enzymes, RNPs, RNAs, non-coding RNAs, helicases, splicing, and processing factors associated with transcription and RNA processing ( Tsai et al, 2020 ; Bertero, 2021 ). It has been proposed that genes and nearby sequences become clustered into a TF by their common affinity for and accessibility to specific transcription factors, RNA polymerases, and other cofactors ( Figure 2D ).…”

“…It has been proposed that genes and nearby sequences become clustered into a TF by their common affinity for and accessibility to specific transcription factors, RNA polymerases, and other cofactors ( Figure 2D ). There is also discussion that such factories enable much higher concentrations of RNA polymerases, transcription factors, and other cofactors to be achieved, thereby increasing the efficiency of transcription ( Sutherland and Bickmore, 2009 ; Cook and Marenduzzo, 2018 ; Tsai et al, 2020 ). Incorporation of genes into transcription factories is not random, but regulated.…”

“…Perturbations of these interactions by incorporation of a genetic variant into the TF, possibly created by variation in transposable elements with binding affinity for transcription factors ( Zhang et al, 2021 ) or one with a different 3D loop structure, could result in each gene being expressed to the same, greater or a lower extent because of the interactions ( Cook and Marenduzzo, 2018 ). Such perturbations may be a major source of phenotypic variation defined by quantitative genetics as non-additive, dominant, overdominant, or epistatic, positively or negatively; and the interfering DNAs would map as QTLs or eQTLs ( Cook and Marenduzzo, 2018 ; Delaneau et al, 2019 ; Peng et al, 2019 ; Zhao et al, 2019 ; Tsai et al, 2020 ). Several examples of correlations between physical interactions and subgenome dominance, colocalization of paralogs and homologs, and biased gene retention after polyploidization in plants are reviewed in Huang et al (2020) .…”

“…Several examples of correlations between physical interactions and subgenome dominance, colocalization of paralogs and homologs, and biased gene retention after polyploidization in plants are reviewed in Huang et al (2020) . Regulation within a transcription factory, therefore, appears to form a “middle layer” of regulation between (a) the molecular control of expression of individual genes and (b) the complex integration of gene networks, physiology, and biochemistry, determining phenotypic traits at the cell and tissue/organ levels ( Tsai et al, 2020 ). The biology of TFs is likely to have profound importance for understanding the genetic basis of traits and plant breeding.…”