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Heterochromatin Definition

Heterochromatin is the densely packed region of chromatin that impairs the transcription of that particular section of DNA. Euchromatin unlike heterochromatin is lightly packed and genes that are actively transcribed are located in this region.

Chromatin comprises DNA and proteins that bind DNA and stabilize it and it is located in the nucleus in the case of eukaryotes. In its condensed state heterochromatin restricts RNA and DNA polymerases to access the DNA strand and thus, it inhibits both DNA transcription and replication. Heterochromatin is of 2 types facultative and constructive heterochromatin. Heterochromatin constitutes only less than 10% of chromatin in humans.

Heterochromatin Structure

The DNA is present as chromatin that is the complex of proteins and DNA in eukaryotes. The proteins involved in this complex are known as histones that wrap the DNA around them. Approximately 200 bp DNA is wrapped around each histone to form nucleosomes which are sets of 8 histones.

Histones present in nucleosomes are H23, H2A, H4, and H3. Their 2 copies each are present in the nucleosome that form an octamer. Nucleosomes are connected by linker DNA that is strands of DNA connecting both nucleosomes.

Heterochromatin, What is Heterochromatin,1

This structure of chromatin that is loosely packed is referred to as the beads-on-string model. The beads represent nucleosomes and the string denotes DNA. It depicts how the nucleosomes are connected by DNA comprising chromatin.

Heterochromatin represents the second level of packaging of DNA into a 30-nm condensed fiber that is helically coiled and whose diameter measures 30nm. This type of heterochromatin is more easily visible in G-banding as it is a more tightly condensed form.

The 30 nm fiber structure can be further compacted and condensed into chromosomes and further condensation leads to the formation of metaphase chromosomes.

A double-strand DNA helix is wrapped around an octamer of histones that form nucleosomes to constitute beads on the string structure of euchromatin. It can be further compacted into heterochromatin that comprises 30 nm fiber. Finally, this can be compacted into chromosomes and metaphase chromosomes.

DNA is in the heterochromatin conformation when it is transcriptionally repressed was the polymerases and other regulatory proteins cannot bind to it in this conformation. The linker DNA in euchromatin is available for transcription, while in heterochromatin conformation it is coiled around nucleosomes and is not exposed.

Heterochromatin Types

There are two Types of Heterochromatin: Constitutive and Facultative

Besides the 2 major types of heterochromatin, there are other kinds that intermediate features of facultative and constitutive heterochromatin.

Constitutive heterochromatin stays in heterochromatin configuration and is more stable and often comprises repeated DNA sequences known as satellite DNA. For instance, this kind of heterochromatin is present in telomeres and centromeres that have structural roles.

Facultative heterochromatin is reversible and can change its structure based on the cell cycle stage. It also consists of repeated sequences of DNA called LINE sequences. For example, the Barr body is the inactivated X chromosomes.

Heterochromatin, Cell Cycle, and Gene Expression

DNA packaging level correlates with cell cycle stages. DNA exists in euchromatin form when it either needs to be transcribed or replicated. When the genes in the DNA do not need to be transcribed or replicated then it exists in heterochromatin conformation.

DNA exists in transcriptionally active forms during the interphase stage, while it is present in metaphase chromosome form in mitosis or meiosis stage when the cell is dividing. Thus by regulating DNA conformation or packaging, gene expression can be controlled.

Housekeeping genes are usually present in the euchromatin region as they need to be constitutively expressed as they are involved in metabolic reactions that sustain the cell. The genes that are not actively expressed occur in heterochromatin configuration. This type of gene regulation is achieved by histone tail modifications.

Acetylation or methylation of histone tails can determine the state the DNA exists in. For example, hypoacetylation on the histone tail will repress DNA expression and change the conformation to heterochromatin.

Heterochromatin Citations
  • Role of H3K9me3 heterochromatin in cell identity establishment and maintenance. Curr Opin Genet Dev . 2019 Apr;55:1-10.
  • Establishment and evolution of heterochromatin. Ann N Y Acad Sci . 2020 Sep;1476(1):59-77.
  • Ten principles of heterochromatin formation and function. Nat Rev Mol Cell Biol . 2018 Apr;19(4):229-244.
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