MAF amplification licenses ERα through epigenetic remodelling to drive breast cancer metastasis.

MAF amplification increases the risk of breast cancer (BCa) metastasis through mechanisms that are still poorly understood yet have important clinical implications. Oestrogen-receptor-positive (ER+) BCa requires oestrogen for both growth and metastasis, albeit by ill-known mechanisms. Here we integrate proteomics, transcriptomics, epigenomics, chromatin accessibility and functional assays from human and syngeneic mouse BCa models to show that MAF directly interacts with oestrogen receptor alpha (ERα), thereby promoting a unique chromatin landscape that favours metastatic spread. We identify metastasis-promoting genes that are de novo licensed following oestrogen exposure in a MAF-dependent manner. The histone demethylase KDM1A is key to the epigenomic remodelling that facilitates the expression of the pro-metastatic MAF/oestrogen-driven gene expression program, and loss of KDM1A activity prevents this metastasis. We have thus determined that the molecular basis underlying MAF/oestrogen-mediated metastasis requires genetic, epigenetic and hormone signals from the systemic environment, which influence the ability of BCa cells to metastasize.

The atypical CDK activator RingoA/Spy1 regulates exit from quiescence in neural stem cells.

In the adult mammalian brain, most neural stem cells (NSCs) are held in a reversible state of quiescence, which is essential to avoid NSC exhaustion and determine the appropriate neurogenesis rate. NSCs of the mouse adult subependymal niche provide neurons for olfactory circuits and can be found at different depths of quiescence, but very little is known on how their quiescence-to-activation transition is controlled. Here, we identify the atypical cyclin-dependent kinase (CDK) activator RingoA as a regulator of this process. We show that the expression of RingoA increases the levels of CDK activity and facilitates cell cycle entry of a subset of NSCs that divide slowly. Accordingly, RingoA-deficient mice exhibit reduced olfactory neurogenesis with an accumulation of quiescent NSCs. Our results indicate that RingoA plays an important role in setting the threshold of CDK activity required for adult NSCs to exit quiescence and may represent a dormancy regulator in adult mammalian tissues.

Engineering Transport in Manganites by Tuning Local Nonstoichiometry in Grain Boundaries.

Interface-dominated materials such as nanocrystalline thin films have emerged as an enthralling class of materials able to engineer functional properties of transition metal oxides widely used in energy and information technologies. In particular, it has been proven that strain-induced defects in grain boundaries of manganites deeply impact their functional properties by boosting their oxygen mass transport while abating their electronic and magnetic order. In this work, the origin of these dramatic changes is correlated for the first time with strong modifications of the anionic and cationic composition in the vicinity of strained grain boundary regions. We are also able to alter the grain boundary composition by tuning the overall cationic content in the films, which represents a new and powerful tool, beyond the classical space charge layer effect, for engineering electronic and mass transport properties of metal oxide thin films useful for a collection of relevant solid-state devices.

Wettability of partially suspended graphene.

The dependence of the wettability of graphene on the nature of the underlying substrate remains only partially understood. Here, we systematically investigate the role of liquid-substrate interactions on the wettability of graphene by varying the area fraction of suspended graphene from 0 to 95% by means of nanotextured substrates. We find that completely suspended graphene exhibits the highest water contact angle (85° ± 5°) compared to partially suspended or supported graphene, regardless of the hydrophobicity (hydrophilicity) of the substrate. Further, 80% of the long-range water-substrate interactions are screened by the graphene monolayer, the wettability of which is primarily determined by short-range graphene-liquid interactions. By its well-defined chemical and geometrical properties, supported graphene therefore provides a model system to elucidate the relative contribution of short and long range interactions to the macroscopic contact angle.