Understanding histone acetyltransferase Rtt109 structure and function: how many chaperones does it take?

Area of Science:

• * Molecular and Cellular Biology
• * Epigenetics and Chromatin Biology
• * Fungal Genetics

Background:

• * Rtt109 (Regulator of Ty1 Transposition 109) is a fungal-specific histone acetyltransferase.
• * It modifies histone H3 at K9, K27, and K56, crucial for nucleosome assembly during DNA replication and repair.
• * Rtt109's activity is uniquely regulated by histone chaperones Vps75 (Vacuolar Protein Sorting 75) and Asf1 (Anti-silencing Function 1).

Purpose of the Study:

• * To elucidate the distinct activation mechanisms of Rtt109 by its cognate histone chaperones, Asf1 and Vps75.
• * To understand how these interactions dictate substrate specificity and acetylation patterns.
• * To investigate the structural basis for Rtt109-Vps75 complex formation and its implications for Rtt109 function.

Main Methods:

• * Biochemical assays to determine Rtt109 activity in the presence of different chaperones.
• * Structural biology techniques (e.g., X-ray crystallography) to visualize Rtt109-chaperone complexes.
• * Genetic studies to assess the in vivo roles of Rtt109, Asf1, and Vps75 in histone modification and cellular processes.

Main Results:

• * Rtt109-Asf1 complex specifically acetylates histone H3 K56.
• * Rtt109-Vps75 complex acetylates histone H3 K9 and K27.
• * Structural data reveals Vps75 positions histone H3 within the Rtt109 active site, though complex stoichiometry remains unclear.

Conclusions:

• * Asf1 and Vps75 activate Rtt109 through divergent molecular pathways, leading to specific histone H3 acetylation events.
• * The distinct roles of these chaperones highlight a sophisticated regulatory network controlling chromatin dynamics.
• * Further structural and biochemical studies are needed to fully resolve the Rtt109-Vps75 complex and its physiological substrates.