PWWP2A/B: Prominent players in the proteomic landscape.

The PWWP domain is a conserved motif unique to eukaryotes, playing a critical role in various cellular processes. Proteins containing the PWWP domain are typically found in chromatin, where they bind to DNA and histones in nucleosomes, facilitating chromatin-associated functions. Among these proteins, PWWP-domain containing proteins 2A and 2B (PWWP2A and PWWP2B), identified during the H2A interactome analysis, are DNA methyltransferase-related proteins, that are structurally disordered, except for their PWWP domain.

microRNA-150 targets major epigenetic repressors and inhibits cell proliferation.

The Polycomb Repressive Complex (PRC) proteins, EZH2 and EZH1 regulate many biological processes by generating the repressive H3K27me3 modifications in the chromatin. However, the factors that regulate the EZH1/EZH2 functions are poorly studied. We identify that the 3'UTRs of EZH2 and EZH1 mRNAs contain the binding sites for the miRNA, miR-150.

CREB acts as a common transcription factor for major epigenetic repressors; DNMT3B, EZH2, CUL4B and E2F6.

CREB signaling is known for several decades, but how it regulates both positive and negative regulators of cell proliferation is not well understood. On the other hand functions of major epigenetic repressors such as DNMT3B, EZH2 and CUL4B for their repressive epigenetic modifications on chromatin have also been well studied. However, there is very limited information available on how these repressors are regulated at their transcriptional level.

De novo methyltransferases: Potential players in diseases and new directions for targeted therapy.

Epigenetic modifications govern gene expression by guiding the human genome on 'what to express and what not to'. DNA methyltransferases (DNMTs) establish methylation patterns on DNA, particularly in CpG islands, and such patterns play a major role in gene silencing. DNMTs are a family of proteins/enzymes (DNMT1, 2, 3A, 3B, and 3L), among which, DNMT1 (maintenance methyltransferase) and DNMT3 (de novo methyltransferases) that direct mammalian development and genome imprinting are highly investigated.

A feedback regulation of CREB activation through the CUL4A and ERK signaling.

CUL4A; an E3 ubiquitin ligase is involved in the degradation of negative regulators of cell cycle such as p21, p27, p53, etc., through polyubiquitination-mediated protein degradation. The functional role(s) of CUL4A proteins on their targets are well characterized; however, the transcriptional regulation of CUL4A, particularly at its promoter level is not yet studied.