Gene expression control by protein deubiquitinases.

Area of Science:

• Molecular Biology
• Epigenetics
• Gene Regulation

Background:

• Protein ubiquitylation regulates diverse eukaryotic cell functions, including gene expression.
• E3 ubiquitin ligases are established in target selection.
• Deubiquitylating enzymes (DUBs) are emerging as critical regulators of ubiquitin-modified cellular processes.

Purpose of the Study:

• To review recent advances in understanding how DUBs regulate chromatin dynamics and gene expression.
• To highlight the integral role of DUBs in the transcription machinery.

Main Methods:

• Discussion of DUB involvement in gene activation and repression.
• Analysis of DUBs' modulation of histone ubiquitylation (H2A, H2B).
• Examination of DUBs within transcriptional coactivator complexes (e.g., SAGA) and gene-silencing machinery (e.g., Polycomb).

Main Results:

• DUBs are integral to transcription, influencing both activation and repression.
• DUBs impact chromatin status by modulating histone H2A and H2B ubiquitylation.
• Specific DUBs are essential for SAGA-mediated gene activation and Polycomb-mediated gene silencing.
• DUBs regulate transcription factors, affecting their levels and localization, as exemplified by p53.
• DUB activity and specificity are often determined by associated partner proteins.

Conclusions:

• DUBs play a pervasive and pivotal role in controlling gene expression.
• DUBs are crucial components of ubiquitin-regulated cellular switches influencing chromatin and transcription.
• The precise molecular mechanisms underlying DUB regulation of gene expression present complex and paradoxical questions.