The structural basis of human Spt16 N-terminal domain interaction with histone (H3-H4)2 tetramer.

Affiliation

State Key Lab of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, PR China. Electronic address: [Email]

Abstract

FACT (Facilitates Chromatin Transactions) is a heterodimeric protein complex involved in RNA polymerase II transcription elongation, playing essential roles in chromatin remodeling during transcription, replication, and DNA damage repair. The FACT subunit hSpt16 is essential for nucleosome reorganization. The N-terminal domain of hSpt16 (hSpt16-NTD) was recently described as a histone (H3-H4)2-binding domain; however, its mode of interaction remains unknown. In this study, we solved the structure of hSpt16-NTD437 at 2.19 Å and found that a long-disordered region (hSpt16-LDR), after the main body of hSpt16-NTD, is a novel histone-binding motif. Furthermore, hSpt16-LDR interaction with (H3-H4)2 is H3 N-terminal tail-independent. Therefore, Spt16-NTD is a histone H3-H4-specific binding domain with a distinct mechanism of interaction between histones and histone chaperones.

Keywords

Aminopeptidase-like domain,FACT,Histone (H3-H4)(2),Histone chaperone,Spt16,