The HMGB1 C-Terminal Tail Regulates DNA Bending

Area of Science:

• Molecular Biology
• Biochemistry
• Genetics

Background:

• High mobility group box protein 1 (HMGB1) is a crucial architectural protein involved in DNA-related processes.
• HMGB1's ability to bend DNA non-sequence specifically is vital for its functions, including transcription and DNA repair.
• HMGB1 comprises two DNA-binding and bending domains (A and B boxes) and a C-terminal acidic tail.

Purpose of the Study:

• To investigate the distinct roles of HMGB1's domains (A box, B box, and C-terminal tail) in DNA bending.
• To elucidate the mechanism by which HMGB1 modulates DNA structure and accessibility.

Main Methods:

• Single-molecule fluorescence resonance energy transfer (smFRET) was employed to quantitatively measure DNA bending.
• Various HMGB1 constructs, including full-length protein and domain-specific mutants, were analyzed.

Main Results:

• Full-length HMGB1 exhibited significant DNA bending, surpassing individual A and B boxes.
• Deletion of the C-terminal tail enhanced DNA bending compared to the full-length protein.
• Mutational analysis indicated the C-terminal tail acts as an intramolecular damper, primarily modulating the B box's interaction with DNA.

Conclusions:

• The C-terminal tail of HMGB1 plays a regulatory role in DNA binding and bending, acting as an intramolecular damper.
• HMGB1's domain interplay, particularly the tail's influence on the B box, is critical for its architectural function in DNA.
• These findings provide a deeper understanding of HMGB1's mechanism in modulating chromatin structure and DNA dynamics.