Linker Histone in Diseases

Abstract

The linker histone is a protein that binds with the nucleosome, which is generally considered to achieve chromatin condensation in the nucleus. Accumulating evidences suggest that the linker histone is essential in the pathogenesis of several diseases. In this review, we briefly introduce the current knowledge of the linker histone, including its structure, characteristics and functions. Also, we move forward to present the advances of the linker histone's association with certain diseases, such as cancer, Alzheimer's disease, infection, male infertility and aberrant immunity situations, focusing on the alteration of the linker histone under certain pathological conditions and its role in developing each disease.

Keywords: Alzheimer's Disease.; Cancer; Chromatin; Linker Histone; Nucleosome.

Figure 1

Nuclear, cytoplasmic and extracellular functions of linker histone. In the nucleus, linker histone is responsible for chromatin condensation and transcriptional activity regulation. In the cytoplasm, linker histones are secreted to trigger the process of apoptosis when DNA double string break occurs. Certain cells, such as macrophages, contain linker histones granules that show antimicrobial activity. Extracellular linker histone forms NET to trap pathogens, or binds with CRP to kill the target pathogen. On the cell membrane of Kupffer cell, linker histone binds TGs and internalizing them.

Figure 2

Linker histone in the pathway of tumorigenesis. Linker histone can respectively bind with CHD8, PTEN and MTA1. H1 binding with CHD8 represses the transcription of p53. H1 normally binds PTEN to promote chromatin condensation and repress the transcription of oncogenes; yet mutated PTEN represses H1 binding and leads to the chromatin relaxation, and promotes the transcription of oncogene in tumor cells. Also, H1 binding with MTA1 alters the transcriptional activity of several genes. These changes might result in the tumorigenesis of the cells through different pathways.

Figure 3

Linker histone's association with several diseases. Linker histone is able to assist the binding and organization of Aβ monomer and form a larger bundle with more fibrils, which might trigger Alzheimer's disease. In the process of spermatogenesis, the failure to replace a subtype of linker histone H1.1 can result in male infertility. Linker histones can induce the occurrence of type I hypersensitivity and is also associated with SLE. Linker histone also defends the organism from pathogen infection by forming NET or binding with CRP. It can also inhibit the replication of viral DNA by hindering in the both ends of the replication fork.