| Abstract |
Chromatin architecture proteins constitute a subclass of nuclear proteins with crucial role in the configuration of chromatin structure, also having impact in the regulation of gene expression. SATB1 is a member of this protein subgroup and has the ability to bind at specific chromosomal regions, called MARs (Matrix Attachment Regions). MARs are characterized by high percentage of AT bases and through them chromatin binds at nuclear matrix, a 3-dimentional filamentous protein network, leading to chromatin loops formation, as a high level of chromatin structure organization. SATB1 acts through the organization-reorganization of chromatin into loops, through which it influences the expression of many genes and consequently the cell phenotype. Expression profile experiments showed that SATB1 is highly expressed in monocytes with stemness phenotype and indeed, these expression levels are dramatically down-regulated after the differentiation of monocytes to macrophages. Consequently, the question of SATB1’s functional role in the biological system of monocytes – macrophages arose. SATB1’s expression in monocytes, before and after differentiation to macrophages, was also studied with DNA-RNA FISH experiments, correlating the expression profile with the chromatin’s structure.
The differentiation process of monocytes to macrophages resembles the one of EMT and it was proved from the experiments in our lab that many EMT-mediators are highly expressed in different stages of monocytes differentiation or after macrophage stimulation with the cytokine TGF-β1. SATB1 can possibly suppress these molecules, till the occurrence of the necessary differentiation or stimulation signal. Moreover, the study of the differentiation process showed that PMA leads to a more intense differentiated phenotype, in case cells are cultured in the absence of it for 24h, after its influence. Further experiments are needed to clarify the exact molecular mechanism of this differentiation process. Furthermore, we have focused our interest in the post-transcriptional regulation of SATB1 by miR-448 and miR-590. Both repress SATB1’s expression in monocytes and T cells, a fact that was not confirmed in luciferase activity experiments. Finally, THP1 human cell line is used for the above experiments and since these cells are derived from acute myeloid leukemia, this study is extended to SATB1’s role in leukemogenesis.
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SATB1, μία αρχιτεκτονική πρωτείνη του πυρήνα και ο ρόλος της στη μονοκυτταρική διαφοροποίηση-λευχαιμογένεση
