Mecp2 Fine-tunes Quiescence Exit by Targeting Nuclear Receptors

Quiescence (G0) maintenance and exit are crucial for tissue homeostasis and regeneration in mammals. Here, we show that methyl-CpG binding protein 2 (Mecp2) expression is cell cycle-dependent and negatively regulates quiescence exit in cultured cells and in an injury-induced liver regeneration mouse model. Specifically, acute reduction of Mecp2 is required for efficient quiescence exit, as deletion of Mecp2 accelerates, while overexpression of Mecp2 delays quiescence exit, and forced expression of Mecp2 after Mecp2 conditional knockout rescues cell cycle reentry. The E3 ligase Nedd4 mediates the ubiquitination and degradation of Mecp2, and thus facilitates quiescence exit. Genome-wide study uncovered the dual role of Mecp2 in preventing quiescence exit by transcriptionally activating metabolic genes while repressing proliferation-associated genes. Particularly, disruption of two nuclear receptors (NRs), Rara or Nr1h3, accelerates quiescence exit, mimicking the Mecp2 depletion phenotype. Our studies unravel a previously unrecognized role for Mecp2 as an essential regulator of quiescence exit and tissue regeneration.

In All Directions

In All Directions

joy is feelinglooking upwardsskies enrapturethe sorry selfand its grievance joy is seeinglooking westwardssocial fracturehealing itselffrom...

Poligraf

In All Directions joy is feeling looking upwards skies enrapture the sorry self and its grievance joy is seeing looking westwards social fracture healing itself from insurgence joy is knowing looking...

Sequential events during the quiescence to proliferation transition establish patterns of follicle cell differentiation in the Drosophila ovary

Summary: Epithelial follicle stem cells in the fly ovary depend on dynamic, axon-like cytoplasmic projections to re-establish cell fate patterning after a period of nutrient restriction.

Priceless Play – 13 July 2019

The Famicase game jam, or A Game By Its Cover, has officially begun. It's about making games that will never exist. Here are some of the best.