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| Identifier |
000433992 |
| Title |
SATB1 mediated chromatin landscape in murine T cells |
| Alternative Title |
Ο ρόλος του SATB1 στην διαμόρφωση της δομής της χρωματίνης στα Τ κύτταρα ποντικού |
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Author
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Παπαματθαιάκης, Διονύσιος Αλέξανδρος Ι.
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Thesis advisor
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Σπηλιανάκης, Χαράλαμπος
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Scientific advisor
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Ταλιανίδης, Ιωάννης
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| Abstract |
Mammalian genomes are characterized by the higher order of their chromatin structure in the
3D nuclearspace astheir genome architecture epigenetically regulates gene expression patterns
via the recruitment of many pioneer factors. Special AT-rich sequence Binding protein 1
(SATB1) is a chromatin organizer which plays a crucial role in T-cell development. The
absence of SATB1 leads to arrested T-cell development and autoimmunity as it is a master
regulator of the T-regulatory cell lineage, governing its early stage development. Although
recent studies have uncovered SATB1’s role in mediating short-range chromatin interactions
in immune specific genes, the mechanism by which SATB1 mediates enhancer-promoter
communication remains elusive. In the present study we focused on delineating the role of
SATB1 in regulating the chromatin landscape of pioneer transcription factors and chromatin
modifiers. We showed that SATB1 physically interacts with the p300 acetyltransferase and
that they both share the same subnuclear localization and therefore they colocalize extensively.
In order to investigate SATB1’s role in enhancer patterning and formation we performed
H3K27ac ChiP-seq experiments in wild type C57BL/6 (WT) and Satb1fl/flCD4-Cre (Satb1
cKO) thymocytes. The overall levels of, the activating for transcription, H3K27ac remain the
same between WT and Satb1 cKO thymocytes, as also supported by immunofluorescence
experiments, but specific immune-related genomic loci are deregulated in the absence of
SATB1 and characterized by either increased or decreased H3K27ac deposition in their
regulatory regions. We also observed the downregulation of immune checkpoint molecules as
well as molecules responsible for the proper development, maturation and cell lineage
commitment in combination with the upregulation of pro-inflammatory cytokines and
transcription factors destined to be expressed in later time points. We conclude that SATB1 is
necessary for the proper spatiotemporal regulation of gene expression of several T cell lineages
and its absence may lead to an autoimmune disease-related phenotype.
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| Language |
English |
| Subject |
Gene regulation |
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Immune system |
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Transcription |
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Ανοσοποιητικό σύστημα |
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Γονιδιακή ρύθμιση |
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Χρωματίνη |
| Issue date |
2020-11-27 |
| Collection
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School/Department--School of Sciences and Engineering--Department of Biology--Post-graduate theses
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Type of Work--Post-graduate theses
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| Permanent Link |
https://elocus.lib.uoc.gr//dlib/4/4/3/metadata-dlib-1605514716-562887-16359.tkl
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| Views |
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