Role of nucleoplasmin family of histone chaperones, NPM1 and NPM2, in the regulation of transcription

Abstract

The DNA, which is the bearer of the hereditary information of a cell, is massively larger in eukaryotic species compared to that in prokaryotes. The size of the genomic DNA generally tends to increase with increasing complexity in the species as we go up higher in the species evolutionary ladder. To contain such a huge length of genomic DNA into the limited confines of the nucleus, the DNA is packaged into a compact structure that is brought about by the action of specific proteins. This superstructure is called the chromatin which consists of a nucleic acid component (the DNA) and a protein component (the histone proteins) (Kornberg 1977). Although primitive forms of genome packaging mechanisms are present in prokaryotes (such as the presence of histone-like proteins in bacteria), basic mechanisms of eukaryotic genome packaging appear to share more commonalities with the archeal counterparts where we find proteins which are structurally similar to eukaryotic histones (Talbert et al. 2019). In eukaryotes, the histones are assembled into an octameric structure comprising of four types of histone proteins in a definite stoichiometry i.e. two dimers of histones H2A and H2B [2(H2A-H2B)] and a tetramer of two H3 and H4 histones each [(H3-H4)2]. A single octamer of these ‘core’ histones is wrapped around by ~146 bp of DNA in roughly two superhelical turns (Luger et al. 1997) to form the nucleosome core particle (NCP) (Section 1.1.2) which is the fundamental unit of chromatin. Two core particles are connected by a linker DNA which is approximately 34 bp long and is associated with another type of histone called H1 or the linker histone that helps in nucleosome locking. The core particle along with a linker DNA constituting roughly 200 bp of DNA in total, is technically called the nucleosome (Oudet et al. 1975), while the nucleosome together with the linker histone is termed as the chromatosome (Simpson 1978) (Section 1.1.2).