MES-­‐4 regulation through cell cycle during development in Caenorhabditis elegans

Abstract

[EN] During development of multicellular organisms differentiation and cell cycle need a tight coordination. This coordination is also orchestrated by changes in the chromatin ladscape. From the initial divisions to the differentiated cells, chromatin switches from an "immature" state that enables stemness and high cell cycle activity, to a "differentiated" state, in which cells have exit cell cycle and are totally differentiated. In the worm Caenorhabditis elegans these two situations are easily distinguished, and regulation of MES proteins maintain this distinction. In this study we centered on the study of the histone methyltransferase MES-4/NSD family. MES-4 maintains the "immature" chromatin landscape, being essential for the survival of germ cells. LIN-35/pRB inhibits mes-4 transcription (Kudron et al., 2013; Wang et al., 2005a), and we found that a KEN box in the MES-4 protein sequence is the target of APC/CFZR-­‐1/Cdh1-­ dependent regulation. Therefore, MES-­‐4 is regulated through cell cycle inhibitors LIN-­‐35 and APC/CFZR-­‐1.This double regulation seems to be important during the development of the worm. Besides, FZR-­‐1 and LIN-­‐35 repression depends on the tissue and developmental stage, being FZR-­‐1 more important in neurons in the head and tail of the worm in early stages, than LIN-­‐35. On the contrary, both regulators cooperate in other tissues, such as the intestine. This cooperation allows a fine-­‐tuned regulation of MES-­‐4 levels during development.