Abstract
Changes in chromatin architecture induced by epigenetic mechanisms are essential for normal cellular processes such as gene expression, DNA repair, and cellular division. Compact chromatin presents a barrier to these processes and is highly regulated by epigenetic markers binding to components of the nucleosome. Histone modifications directly influence chromatin dynamics and facilitate recruitment of additional factors such as chromatin remodelers and histone chaperones. One member of this last class of factors, FACT (facilitates chromatin transcription), is categorized as a histone chaperone critical for nucleosome reorganization during replication, transcription, and DNA repair. Significant discoveries regarding the role of histone chaperones and specifically FACT have come over the past dozen years from a number of independent laboratories. Here, we review the structural and biophysical basis for FACT-mediated nucleosome reorganization and discuss up-to-date models for FACT function.
Highlights
Chromatin is a densely packed and tightly regulated nucleoprotein complex that stores the genetic material of a cell in a stable yet readily accessible form
How is the FACT heterocomplex recruited to specific sites in chromatin, and by what means is FACT turned “on” and “off?” Here, we focus on the proposed mechanistic models for this histone chaperone and on direct nucleosome reorganization functions of FACT
Some aspects of the two models, which pertain to the h/yFACT architecture, are undoubtedly different, such as the role Nhp6 plays in yFACT recruitment to nucleosomes
Summary
The human (h) FACT complex was first identified in 1998 as a factor essential for transcriptional elongation through chromatin [6]. The Pob protein includes two structural domains similar to the SSRP1 NTD/DD and MD with a C-terminal intrinsically disordered region [19]. The crystal structure of the first 111 residues of the Pob NTD/DD (220 residues total) displays a single pleckstrin homology (PH) domain (Protein Data Bank code 3F5R) (Fig. 2, lower panel). An additional Nhp6a structure in complex with SRY DNA, which contains a recognition site for HMG box proteins [30], has been solved using solution NMR (Protein Data Bank code 1J5N) (Fig. 2, lower panel) [30]. Physical modification of the Spt and SSRP1 subunits efficiently provides an additional level of control over FACTinduced nucleosome reorganization and chromatin dynamics
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