Towards understanding the role of HILS1 in chromatin remodeling during spermiogenesis

Abstract

Genomic DNA in eukaryotic nucleus is compactly packaged to generate a highly ordered 3D hierarchical structure known as chromatin [1, 2]. Kornberg [5] proposed that chromatin is composed of a flexible chain of repeating units of 100A˚ diameter [5]. These units were termed as “nucleosomes” by Oudet et al. [6]. On further digestion of nucleosome, a nucleosome core was obtained. Nucleosome is the fundamental repeating unit of chromatin which comprises of 146 base pairs of DNA wrapped in ~1.65 left superhelical turns around an octamer of histone proteins with a pitch of ~26.5A˚ and a radius of ~ 42.5A˚ [7]. Electron microscopy and X-ray diffraction techniques suggested that this particle is a disk, 57A˚ thick and 110A˚ in diameter, and that the DNA is wound around the histone core [8]. Octamer consists of 2 molecules each of core histones H2A, H2B, H3 and H4. Nucleosomes are connected to each other by linker DNA. Linker histone H1 is bound to this linker DNA region. The nucleosomal array looks like a ‘beads-on-a-string’ with a diameter of 11nm and it represents first level of chromatin organization [7]. The binding of linker histone H1 helps in the organization of nucleosome arrays into a more condensed 30nm fibre which represents second level of chromatin organization [9].The nucleosome thereby shapes the DNA molecule both at the atomic level through DNA bending, and on the much larger scale by forming higher order structure [10]. The characteristics of an individual nucleosome depends mainly on the DNA sequences iNcorporated, post translational modifications of histones, and on the buffer conditions like ionic strength, divalent ion concentration etc. [1, 11]. The final compaction of chromatin results in the metaphase/meiotic chromosome which exhibits 10,000–20,000 fold compaction in somatic cell’s nucleus [12].