Structural basis for histone variant H3tK27me3 recognition by PHF1 and PHF19

Area of Science:

• Epigenetics and gene regulation
• Molecular biology
• Chromatin biology

Background:

• Polycomb repressive complex 2 (PRC2) silences genes, notably *Hox* genes, during development.
• Polycomb-like proteins PHF1, MTF2, and PHF19 are crucial for PRC2 activity in embryonic stem cells.
• Previous studies indicated Tudor domains of PHF1/19 read H3K36me3 in vitro, but cellular localization data suggested co-localization with H3K27me3.

Purpose of the Study:

• To investigate the interaction of PHF1 and PHF19 with histone modifications in testis.
• To elucidate the molecular basis for the recognition of specific histone marks by PHF1 and PHF19 Tudor domains.
• To determine if H3tK27me3 is a physiological ligand for PHF1/19.

Main Methods:

• Co-localization studies of PHF1 with histone marks in testis.
• In vitro binding assays using purified Tudor domains of PHF1 and PHF19.
• X-ray crystallography to determine complex structures of PHF1/PHF19 Tudor domains with H3tK27me3.

Main Results:

• PHF1 co-localizes with H3t in testis.
• The Tudor domain of PHF1 preferentially binds H3tK27me3 over canonical H3K27me3 in vitro.
• Structural analysis revealed the molecular basis for PHF1 and PHF19's selective recognition of H3tK27me3.

Conclusions:

• PHF1 and PHF19 exhibit a preference for H3tK27me3 over canonical H3K27me3.
• The structural data provides insight into the mechanism of H3tK27me3 recognition.
• H3tK27me3 is proposed as a potential physiological ligand for PHF1 and PHF19.