Functional mechanisms of human transcriptional coactivator PC4, a bona fide nonhistone component of chromatin

Abstract

The Eukaryotic genome is organized into a highly complex nucleoprotein structure, chromatin, which is composed of DNA, wrapped around a core histone octamer and a diverse group of nonhistone proteins involved in maintaining the cellular homeostasis. The dynamic chromatin organization is regulated by three different groups of factors: (i) histone and nonhistone modifying enzymes; (ii) ATP-dependent chromatin remodelling enzymes; (iii) histone chaperones. The posttranslational modifications of the core histones and other nonhisone chromatin proteins (including linker histone H1) lead to differential functional consequences (Wolffe et al, 1997; Agresti and Bianchi, 2003; Bustin, 2001; Garcia-Ramirez et al, 1992). The ATP-dependent chromatin remodeling and histone chaperones (for core or linker histones) also contribute to the organization of the dynamic chromatin (Vignali et al, 2000; Loyola and Almouzni, 2004; Saha et al, 2006). The ATP-dependent chromatin remodeling machinery is responsible for differential positioning of the DNA over the core octamer. Thus the regulatory DNA sequences can be accessed by several factors transiently without altering the overall chromatin structure. The histone chaperones are anionic cellular proteins that help in proper assembly and disassembly of chromatin, preventing nonspecific aggregation. The functional diversity of this class of proteins ranges from histone storage and transport, transcription regulation and repair. The chromatin fiber bridging proteins (eg. Sir3p, Tup1, MENT etc) (Gavin and Simpson, 1997; Georgel et al, 2001, Springhetti et al, 2003) and other nonhistone chromatin associated proteins (eg. HMGs, HP1, MeCP2, PARP1 etc) (Agresti and Bianchi, 2003; Bustin, 2001; Catez et al, 2004; Pallier et al, 2003; Li et al, 2002; Kriaucionis and Bird, 2003; Kim et al, 2004) help in chromatin compaction or decompaction through their direct interaction with core-histones and/or DNA. These proteins may also compete or cooperate with histone H1 during this process. The interaction of histone H1 with the nucleosomes stabilizes the higher order compact chromatin structure, restricting the ability of the regulatory factors to access their chromatin binding sites (Allan et al, 1981; Thomas, 1999; Wolffe et al, 1997). Taken together the dynamicity of the chromatin is mediated by a diverse repertoire of factors orchestrating the events towards a destined cellular fate.