Ricerc@Sapienza

The myogenic factor MyoD regulates skeletal muscle differentiation by interacting with a variety of chromatin-modifying complexes. Although MyoD can induce and maintain chromatin accessibility at its target genes, its binding and trans-activation ability can be limited by some types of not fully characterized epigenetic constraints. In this work we analysed the role of PARP1 in regulating MyoD-dependent gene expression. PARP1 is a chromatin-associated enzyme, playing a well recognized role in DNA repair and that is implicated in transcriptional regulation.

1. ABSTRACT

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive blood cancer caused by the deregulation of key T-cell developmental pathways, including Notch signaling. Aberrant Notch signaling in T-ALL occurs by NOTCH1 gain-of-function mutations and by NOTCH3 overexpression. Although NOTCH3 is assumed as a Notch1 target, machinery driving its transcription in T-ALL is undefined in leukemia subsets lacking Notchl activation.

Ethanol exposure during gestation is an early life stressor that profoundly dysregulates structure and functions of the embryonal nervous system, altering the cognitive and behavioral development. Such dysregulation is also achieved by epigenetic mechanisms, which, altering the chromatin structure, redraw the entire pattern of gene expression. In parallel, an oxidative stress response at the cellular level and a global upregulation of neuroendocrine stress response, regulated by the HPA axis, exist and persist in adulthood.

During the past decades, several discoveries have established the role of epigenetic modifications and cellularmicroenvironment in tumor growth and progression. One of the main representatives concerning epigenetic modification is the polycomb group (PcG). It is composed of different highly conserved epigenetic effector proteins preserving, through several post-translational modifications of histones, the silenced state of the genes implicated in a wide range of central biological events such as development, stem cell formation, and tumor progression.

This work highlights recent studies in epigenetic mechanisms that play a role in alcoholism, which is a complex multifactorial disorder. There is a large body of evidence showing that alcohol can modify gene expression through epigenetic processes, namely DNA methylation and nucleosomal remodeling via histone modifications. In that regard, chronic exposure to ethanol modifies DNA and histone methylation, histone acetylation, and microRNA expression. The alcohol-mediated chromatin remodeling in the brain promotes the transition from use to abuse and addiction.

Gestational Diabetes Mellitus (GDM) is defined as glucose intolerance that develops in the second or third trimester of pregnancy. GDM can lead to short-term and long-term complications both in the mother and in the offspring. Diagnosing and treating this condition is therefore of great importance to avoid poor pregnancy outcomes. There is increasing interest in finding new markers with potential diagnostic, prognostic and therapeutic utility in GDM.