dexamethasone acetate br Experimental section br Results and

Experimental section
Results and discussion
Conclusion The evaluation of the inhibitory potential of these derivatives towards eight kinases showed that the brominated hybrids (3k) and (3l) are the most active against the PIM1 and CLK1 kinases. The methylation of the nitrogen dexamethasone acetate of the isatin allows the brominated hybrid (3l) to gain in selectivity. These promising results motivate us to refine our structures to further enhance their activity and selectivity towards a wider range of kinases.
Funding This work was supported by the Ministry of Higher Education and Scientific Research of Algeria, (PNE/Doctorant/France/2016–2017).
Conflicts of interest
Introduction Epigenetic phenomena are heritable changes in gene expression or function that can persist throughout many cell divisions without alterations in primary DNA sequences. By regulating differential gene expression, epigenetic processes are able to direct cells with identical genomes to become distinct cell types in humans and other multicellular organisms. However, with the exception of DNA methylation, little is known about the molecular pathways leading to epigenetic inheritance (Bonasio et al., 2010, Martin and Zhang, 2007). Prior research has shown that epigenetic events play particularly important roles in ensuring both proper maintenance and differentiation of several stem cell populations. Many types of adult stem cells undergo asymmetric cell division to generate a self-renewed stem cell and a daughter cell that will subsequently differentiate (Betschinger and Knoblich, 2004, Clevers, 2005, Inaba and Yamashita, 2012, Morrison and Kimble, 2006). Mis-regulation of this balance leads to many human diseases, ranging from cancer to tissue dystrophy to infertility. However, the mechanisms of stem cell epigenetic memory maintenance as well as how loss of this memory contributes to disease remain unknown. Recently, we found that during the asymmetric division of the Drosophila male germline stem cell (GSC), the pre-existing histone 3 (H3) is selectively segregated to the self-renewed GSC daughter cell whereas newly synthesized H3 is enriched in the differentiating daughter cell known as a gonialblast (GB) (Tran et al., 2012) (Figure 1A). In contrast, the histone variant H3.3, which is incorporated in a replication-independent manner, does not exhibit such an asymmetric pattern. Furthermore, we found that asymmetric H3 inheritance occurs specifically in asymmetrically dividing GSCs, but not in the symmetrically dividing progenitor cells. These findings demonstrate that global asymmetric H3 histone inheritance possesses both molecular and cellular specificity. We proposed the following model to explain our findings. First, the cellular specificity exhibited by the H3 histone suggests that global asymmetric histone inheritance occurs uniquely in a cell-type (GSC) where the mother cell must divide to produce two daughter cells each with a unique cell fate. Because this asymmetry is not observed in symmetrically dividing GB cells, we propose asymmetric histone inheritance to be a phenomenon specifically employed by GSCs to establish unique epigenetic identities in each of the two daughter cells. Second, as stated previously, a major difference between H3 and H3.3 is that H3 is incorporated to chromatin during DNA replication, while H3.3 variant is incorporated in a replication-independent manner. Because this asymmetric inheritance mode is specific to H3, we propose a two-step model to explain asymmetric H3 inheritance: (1) prior to mitosis, pre-existing and newly synthesized H3 are differentially distributed on the two sets of sister chromatids, and (2) during mitosis, the set of sister chromatids containing pre-existing H3 is segregated to GSCs, while the set of sister chromatids enriched with newly synthesized H3 is segregated to the GB that differentiates (Tran et al., 2012, Tran et al., 2013) (Figure 1B).