Epigenetics: What are Histones ?

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Source: https://www.cusabio.com/histones.html

What Are Histones?

DNA is like a magical, intricately coiled cable of life, but its wizardry lies in collaboration with histones, which magically compresses the 2-meter-long DNA within a tiny 6-micron cell, storing the secrets of genetic information.

1. What Are Histones?

Histone was first discovered by Albrecht Kossel in 1884 [1]. Histones are a family of alkaline proteins found in the nuclei of eukaryotic cells and are the major structural components of chromosomes.

They are rich in lysine and arginine residues and thus positively charged, enabling their tight binding to the negatively charged DNA to form chromatin.

2. Structure and Classes of Histones

Histones are mainly divided into two classes: core histones and linker histones. Core histones include four members: H2A, H2B, H3, and H4. Linker histones include H1 or its homologue H5. In eukaryotes, the core histones are usually synthesized during DNA replication, reaching peak expression in the S phase.

All core histones show a strong conservation across species, from yeast to humans.

They feature a C-terminal histone-fold domain (HFD) that is involved in histone octamer formation and an unstructured N-terminal tail that protrudes from the core particle and is subjected to various post-translational modifications (PTMs).

Within a nucleosome, the core histone consists of a (H3-H4) 2 tetramer flanked by two H2A-H2B dimers, forming an octamer around which 147 bp of DNA is spooled twice.

The interaction between H1 and the nucleosome, along with additional DNA stretches at the entry/exit sites of the nucleosome, results in the formation of the beads-on-a-string chromosome and contributes to the establishment of higher-order chromatin structure.

Six nucleosomes, in conjunction with H1 histones, combine to form a solenoid structure, which is subsequently coiled around a scaffold, which is further coiled to assemble the chromosomal matrix.

3. Histone Variants

Histone variants are variations or slightly different forms of histone proteins, particularly core histones. They share structural similarities with the core histones but have distinct properties and functions.

They impart distinct structural and physical diversities to nucleosomes, either by wrapping more or less DNA or by changing nucleosome stability.

Histone variants contribute to the complexity and versatility of chromatin structure and epigenetic genome regulation in eukaryotic cells.

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