The adaptive immune response is fully dependent on the proper T cell development. Committed lymphoid progenitors in the thymus undergo a series of events including positive and negative selection, resulting in naïve T cells. The second pillar of the T cell function consists of the activation and differentiation processes of naive CD4+ precursor cells in response to cues provided by antigen presenting cells. The different CD4 T cell fates are determined via complex and cross-interactive networks consisted of cytokines and transcription factors. The co-expression of the latter affects the functional capabilities and the flexibility of the different CD4 T cell subsets.
Recently, the three-dimensional (3D) organization of chromatin has been recognized as a crucial regulator of gene expression. The factor CTCF has been proposed as a major player for establishing the 3D structure of genomes. However, the complex environment of developing T cells requires additional master regulators to operate the 3D interactome. The special AT-rich sequence binding protein 1 (SATB1) is a well-known genome organizer that has also been suggested to play this role. In the cell nucleus, SATB1 creates a cage-like protein structure providing a physical prop for DNA and also serving as a platform for other protein complexes. Its ability to create tetramers facilitates genome folding by creating DNA loops and such looping events may constitute one of the major mechanisms for gene expression regulation. The importance of SATB1 in thymocyte development has already been established and affects the proper function of the adaptive immune system.
SATB1 undergoes isoform-specific phase transitions in T cells
Tomas Zelenka, Petros Tzerpos, Giorgos Panagopoulos, Konstantinos Tsolis, Dionysios-Alexandros Papamatheakis, Vassilis M. Papadakis, David Stanek, Charalampos Spilianakis
bioRxiv 2021.08.11.455932; doi: https://doi.org/10.1101/2021.08.11.455932
The 3D enhancer network of the developing T cell genome is controlled by SATB1
Tomas Zelenka, Antonios Klonizakis, Despina Tsoukatou, Sören Franzenburg, Petros Tzerpos, Dionysios-AlexandrosPapamatheakis, Ioannis-Rafail Tzonevrakis, ChristoforosNikolaou, Dariusz Plewczynski, Charalampos Spilianakis
bioRxiv 2021.07.09.451769; doi: https://doi.org/10.1101/2021.07.09.451769
HiChIP and Hi-C Protocol Optimized for Primary Murine T Cells.
Zelenka T, Spilianakis C.
Methods Protoc. 2021; 4(3):49. doi: https://doi.org/10.3390/mps4030049
landscape in T cells.
Zelenka T & Spilianakis C.G.
Nucleus 2020; 11: 117-131; doi: https://doi.org/10.1080/19491034.2020.1775037
Conservation of microRNA Gene Localization at the Nuclear Periphery.
Salataj E, Stathopoulou C, Hafþórsson RA, Nikolaou C, Spilianakis C.G.
PLoS One 2019; 14(11):e0223759. https://doi.org/10.1371/journal. pone.0223759
Long non-coding RNA SeT and miR-155 regulate the Tnfα
gene allelic expression profile.
Stathopoulou C, Kapsetaki M, Stratigi K, Spilianakis C.
PLoS One 2017; 14;12(9):e0184788. doi: https://doi.org/10.1371/journal.pone.0184788
Coordinated Regulation of miR-155 and
miR-146a Genes during Induction of Endotoxin Tolerance in Macrophages.
Doxaki C., Kampranis S.C., Eliopoulos A.G., Spilianakis C., Tsatsanis C.
J Immunol. 2015; 195(12):5750-5761. doi: 10.4049/jimmunol.1500615
Spatial proximity of homologous alleles
and long noncoding RNAs regulate a switch in allelic gene expression.
Stratigi K., Kapsetaki M., Aivaliotis M., Town T., Flavell RA., Spilianakis CG.
Proc Natl Acad Sci USA 2015; 112(13):E1577-1586 doi: https://doi.org/10.1073/pnas.1502182112
Higher order chromatin organization controls the regulation of genome activity and serves as an additional epigenetic mechanism that modulates cellular functions and gene expression programs in diverse biological processes. Spatial positioning of different gene loci can be directly linked to gene expression while other findings confirm that deregulation of nuclear architecture can be linked to severe diseases. Apart from the organization of chromatin per se, the metazoan interphase nuclei are also functionally compartmentalized, with different repressive and active nuclear sub-compartments governing gene expression. Compartments such as the nuclear lamina and the nucleolus gather repressed genes, while RNA Pol II factories attract expressing genes. Allelic interactions and gene repositioning with functional importance are common during the regulation of immune responses. Chromatin loops, constituting Lamina Associated Domains (LADs), modify their proximity to the nuclear lamina offering a plausible explanation to past reports documenting the relocalization of gene loci, upon their transcriptional activation, away from the nuclear periphery, further supporting the implication of nuclear lamina in gene silencing.