Regulation of gene expression

About: Regulation of gene expression is a research topic. Over the lifetime, 85456 publications have been published within this topic receiving 5832845 citations. The topic is also known as: GO:0010468 & gene expression regulation.

Interchromosomal associations between alternatively expressed loci

Abstract: The T-helper-cell 1 and 2 (TH1 and TH2) pathways, defined by cytokines interferon-g (IFN-g) and interleukin-4 (IL-4), respectively, comprise two alternative CD4 þ T-cell fates, with functional consequences for the host immune system. These cytokine genes are encoded on different chromosomes. The recently described TH2 locus control region (LCR) coordinately regulates the TH2 cytokine genes by participating in a complex between the LCR and promoters of the cytokine genes Il4, Il5 and Il13. Although they are spread over 120kilobases, these elements are closely juxtaposed in the nucleus in a poised chromatin conformation. In addition to these intrachromosomal interactions, we now describe interchromosomal interactions between the promoter region of the IFN-g gene on chromosome 10 and the regulatory regions of the TH2 cytokine locus on chromosome 11. DNase I hypersensitive sites that comprise the TH2 LCR developmentally regulate these interchromosomal interactions. Furthermore, there seems to be a cell-type-specific dynamic interaction between interacting chromatin partners whereby interchromosomal interactions are apparently lost in favour of intrachromosomal ones upon gene activation. Thus, we provide an example of eukaryotic genes located on separate chromosomes associating physically in the nucleus via interactions that may have a function in coordinating gene expression.

Single-cell NF-κB dynamics reveal digital activation and analogue information processing

Abstract: Cells operate in dynamic environments using extraordinary communication capabilities that emerge from the interactions of genetic circuitry. The mammalian immune response is a striking example of the coordination of different cell types 1 . Cell-to-cell communicationisprimarilymediatedbysignallingmoleculesthat form spatiotemporal concentration gradients, requiring cells to respond to a wide range of signal intensities 2 . Here we use highthroughputmicrofluidiccellculture 3 andfluorescencemicroscopy, quantitative gene expression analysis and mathematical modelling to investigate how single mammalian cells respond to different concentrations of the signalling molecule tumour-necrosis factor (TNF)-a, and relay information to the gene expression programs by means of the transcription factor nuclear factor (NF)-kB. We measured NF-kB activity in thousands of live cells under TNF-a doses covering four orders of magnitude. We find, in contrast to population-level studies with bulk assays 2 , that the activation is heterogeneous and is a digital process at the single-cell level with fewer cells responding at lower doses.Cells also encode a subtle set of analogue parameters to modulate the outcome; these parameters include NF-kB peak intensity, response time and number ofoscillations.Wedevelopedastochasticmathematicalmodelthat reproduces both the digital and analogue dynamics as well as most gene expression profiles at all measured conditions, constituting a broadly applicable model for TNF-a-induced NF-kB signalling in various types of cells. These results highlight the value of highthroughput quantitative measurements with single-cell resolution in understanding how biological systems operate. Most of the information on cell signalling has been obtained from

Nuclear organization of the genome and the potential for gene regulation

Abstract: Much work has been published on the cis-regulatory elements that affect gene function locally, as well as on the biochemistry of the transcription factors and chromatin- and histone-modifying complexes that influence gene expression. However, surprisingly little information is available about how these components are organized within the three-dimensional space of the nucleus. Technological advances are now helping to identify the spatial relationships and interactions of genes and regulatory elements in the nucleus and are revealing an unexpectedly extensive network of communication within and between chromosomes. A crucial unresolved issue is the extent to which this organization affects gene function, rather than just reflecting it.