p300/CBP-associated factor drives DEK into interchromatin granule clusters

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• DEK protein is implicated in cancer and autoimmune diseases.
• DEK participates in transcriptional repression, mRNA processing, and chromatin remodeling.
• DEK's sub-nuclear localization and function remain controversial.

Purpose of the Study:

• To investigate the role of DEK acetylation in its cellular localization and function.
• To elucidate the mechanism by which DEK interacts with different sub-nuclear compartments.

Main Methods:

• In vivo acetylation studies of DEK at N-terminal lysine residues.
• Assays to measure DEK's affinity for DNA elements.
• Studies on DEK localization upon deacetylase inhibition and acetylase overexpression.
• Testing the effect of a P/CAF inhibitor on DEK localization.

Main Results:

• DEK undergoes in vivo acetylation within its first 70 N-terminal amino acids.
• Acetylation reduces DEK's DNA binding affinity, supporting its role in transcriptional repression.
• Deacetylase inhibition causes DEK accumulation in interchromatin granule clusters (IGCs).
• P/CAF acetylase overexpression drives DEK into IGCs, which is blocked by a P/CAF inhibitor.

Conclusions:

• Acetylation directly regulates DEK's relocation to IGCs, explaining its function in distinct sub-nuclear compartments.
• This acetylation-dependent mechanism provides a novel understanding of DEK's diverse roles.
• Targeting acetylation may offer therapeutic strategies for DEK-associated malignancies and autoimmune diseases.