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.
