Regulation of chromatin structure and function: insights into the histone chaperone FACT

Abstract

In eukaryotic cells, changes in chromatin accessibility are necessary for chromatin to maintain its highly dynamic nature at different times during the cell cycle. Histone chaperones interact with histones and regulate chromatin dynamics. Facilitates chromatin transcription (FACT) is an important histone chaperone that plays crucial roles during various cellular processes. Here, we analyze the structural characteristics of FACT, discuss how FACT regulates nucleosome/chromatin reorganization and summarize possible functions of FACT in transcription, replication, and DNA repair. The possible involvement of FACT in cell fate determination is also discussed.Abbreviations: FACT: facilitates chromatin transcription, Spt16: suppressor of Ty16, SSRP1: structure-specific recognition protein-1, NTD: N-terminal domain, DD: dimerization domain, MD: middle domain, CTD: C-terminus domain, IDD: internal intrinsically disordered domain, HMG: high mobility group, CID: C-terminal intrinsically disordered domain, Nhp6: non-histone chromosomal protein 6, RNAPII: RNA polymerase II, CK2: casein kinase 2, AID: acidic inner disorder, PIC: pre-initiation complex, IR: ionizing radiation, DDSB: DNA double-strand break, PARlation: poly ADP-ribosylation, BER: base-excision repair, UVSSA: UV-stimulated scaffold protein A, HR: homologous recombination, CAF-1: chromatin assembly factor 1, Asf1: anti-silencing factor 1, Rtt106: regulator of Ty1 transposition protein 106, H3K56ac: H3K56 acetylation, KD: knock down, SETD2: SET domain containing 2, H3K36me3: trimethylation of lysine36 in histone H3, H2Bub: H2B ubiquitination, iPSCs: induced pluripotent stem cells, ESC: embryonic stem cell, H3K4me3: trimethylation of lysine 4 on histone H3 protein subunit, CHD1: chromodomain protein.

Keywords: FACT; Histone chaperone; cell fate; chromatin dynamics.

Graphical abstract

Figure 1.

Domain organization of hFACT and yFACT. The heterodimeric hFACT complex is composed of the hSpt16 (cyan) and SSRP1 (green) subunits, through an interaction (gray) between the DD domain of hSPT16 (cyan) and the NTD/DD domain of SSRP1. In yeast, ySpt16 (cyan) and Pob3 (blue) subunits form the yFACT complex. (3D structures are from the UniProt website)

Figure 2.

Working models of FACT function. (a) The “dimer eviction model”, in which FACT actively removes H2A–H2B from nucleosomes to enhance DNA accessibility. (b) The “non-eviction model”, in which FACT makes the nucleosome structure more relaxed and dynamic without the eviction of H2A–H2B

Figure 3.

The role of FACT in DNA damage repair. (a) FACT and RSC work together to promote DNA damage repair during the initial steps of the base excision repair process. (b) FACT acts as an early factor in UV-induced DNA damage and recruits UVSSA during the transcription-coupled nucleotide excision repair (TC-NER) process. (c) FACT participates in the exchange of histone variant H2A.X with conventional H2A during the DDSB repair process. (d) FACT promotes the homologous recombination repair process