The androgen receptor (AR) is a key molecule involved in prostate cancer (PC) development and progression. Post-translational modification of the AR by co-regulator proteins can modulate its transcriptional activity. To identify which demethylases might be involved in AR regulation, an siRNA screen was performed to reveal that the demethylase, KDM4B, may be an important co-regulator protein. KDM4B enzymatic activity is required to enhance AR transcriptional activity; however, independently of this activity, KDM4B can enhance AR protein stability via inhibition of AR ubiquitination. Importantly, knockdown of KDM4B in multiple cell lines results in almost complete depletion of AR protein levels. For the first time, we have identified KDM4B to be an androgen-regulated demethylase enzyme, which can influence AR transcriptional activity not only via demethylation activity but also via modulation of ubiquitination. Together, these findings demonstrate the close functional relationship between AR and KDM4B, which work together to amplify the androgen response. Furthermore, KDM4B expression in clinical PC specimens positively correlates with increasing cancer grade (P < 0.001). Consequently, KDM4B is a viable therapeutic target in PC.

The lysine methyltransferase SETD6 modifies the histone variant H2AZ, a key component of nuclear receptor-dependent transcription. Herein, we report the identification of several factors that associate with SETD6 and are implicated in nuclear hormone receptor signaling. Specifically, SETD6 associates with the estrogen receptor α (ERα), histone deacetylase HDAC1, metastasis protein MTA2, and the transcriptional co-activator TRRAP. Luciferase reporter assays identify SETD6 as a transcriptional repressor, in agreement with its association with HDAC1 and MTA2. However, SETD6 behaves as a co-activator of several estrogen-responsive genes, such as PGR and TFF1. Consistent with these results, silencing of SETD6 in several breast carcinoma cell lines induced cellular proliferation defects accompanied by enhanced expression of the cell cycle inhibitor CDKN1A and induction of apoptosis. Herein, we have identified several chromatin proteins that associate with SETD6 and described SETD6 as an essential factor for nuclear receptor signaling and cellular proliferation.

The COVID-19 pandemic has revealed the Eastern Mediterranean Region's food system's fragility posing severe challenges to maintaining healthy sustainable lifestyle. The aim of this cross-sectional study (N = 13,527 household's family members, mean age: 30.3 ±11.6, 80% women) is to examine the impact of the COVID-19 pandemic on food consumption patterns and household's dietary diversity in 10 Eastern Mediterranean countries. A food frequency questionnaire was used to investigate the consumption patterns along with the calculation of the Food Consumption Score (FCS), a proxy indicator of dietary diversity. Data collected on cooking attitudes, shopping and food stock explore the community mitigation measures. In the overall population, before and during the pandemic, most food groups were consumed less or equal to 4 times per week. As evident from our findings and considering that the pandemic may be better, but it's not over, small to moderate changes in food consumption patterns in relatively short time periods can become permanent and lead to substantial poor dietary diversity over time. While it is a priority to mitigate the immediate impact, one area of great concern is the long-term effects of this pandemic on dietary patterns and dietary diversity in Eastern Mediterranean households. To conclude, the COVID-19 crisis revealed the region's unpreparedness to deal with a pandemic. While the aggressive containment strategy was essential for most countries to help prevent the spread, it came at a high nutritional cost, driving poor dietary diversity.