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    Analysis of human, murine and avian erythroid differentiation : modification of the proteome and histones.

    Marjorie Leduc

     

    Tuesday 23 March 15 pm

    Institut Cochin (by videoconference)

     

    Supervisor: Patrick Mayeux

    Team: Hématopoïèse Normale et Pathologique

    Department : Développement, Reproduction, Cancer (DRC)

     

    Abstract:

    Terminal erythroid differentiation (TED) is the transformation of progenitors to red cells. I used proteomic analysis to characterize the evolution of the proteome of murine, human and avian cells during TED. From 5000 to 8000 proteins were quantified in copy numbers per cell in these models. The main results are :

    1- Most differences between human and murine TED observed at the transcriptome level are largely buffered at the proteome level.

    2- The avian erythroblasts show molecular features very different of those of murine and human erythroid cells such as an increase of KIT expression during TED.

    3- Unlike murine cell lines usually used to study TED, G1ER and MEL, that only partially differentiate, MEDEP cells realize a complete TED, similar to that of primary cells.

    4- Using different analysis strategies some of which being based on the use of heavy isotopes (SuperSILAC), I show that, unlike a hypothesis proposed by some teams, the total quantity of nuclear histones doesn’t decrease during TED.

    5- Using a multiple digestion method, I identified isoformes of histones in erythroid cells and their evolution during TED. I performed an analysis of their post translational modifications showing a temporary increase of the phosphorylation of residue 18 of histones H1.3, H1.4, H1.5, and many changes of post translational modifications of histone H3 during TED.