Login processing...

Chapter 5: DNA and Chromosome Structure Back To Chapter

5.11: Position-effect Variegation

TABLE OF
CONTENTS

JoVE Core
Molecular Biology

A subscription to JoVE is required to view this content.

Education

Position-effect Variegation

Previous Video Next Video

Previous Video
5.10: Karyotyping

Next Video
5.12: Histone Modification

Embed Languages Add to Favorites ADD TO PLAYLIST

English 中文 Français Português Türkçe Русский العربية Italiano

TRANSCRIPT

In a eukaryotic cell, DNA associates with various proteins to form a tightly packed, highly condensed structure called chromatin. Chromatin is divided into two types, depending upon the level of compaction.

Heterochromatin, concentrated in the centromeres and telomeres, is highly condensed, gene-poor, and infrequently transcribed into RNA.

In contrast, euchromatin, which constitutes a majority of the chromosomal material, is less condensed, gene-rich, and actively transcribed.

Heterochromatin and euchromatin are separated by barrier DNA sequences. These sequences prevent the spread of heterochromatin and maintain stable gene expression patterns.

During DNA rearrangement events, such as transposition, a piece of euchromatin can be translocated near a heterochromatin region without any adjacent DNA barrier sequences.

In such events, genes that are typically active are ‘silenced’ or ‘inactivated.’ This phenomenon is known as the ‘position effect.’

For example, in Drosophila, red eye color is encoded by the ‘white’ gene. Occasionally, ‘white’ is moved near a heterochromatin region without any DNA barrier sequences in between.

When flies inherit this genotype, during their early embryonic stages when heterochromatin is first formed, the absence of barrier DNA allows the heterochromatin to spread into the neighboring euchromatin.

However, spreading occurs to different extents in different embryonic cells. This variation in heterochromatin spreading yields cells that exhibit two distinct phenotypes- one which actively expresses the ‘white’ gene and others that do not.

Once established, all of that cell’s progeny inherit this state. This results in the mottled, or mosaic, eyes in the adult flies.

This phenotype variegation, caused by the gene silencing mediated by a change in the position of the ‘white’ gene within the chromosome, is called ‘position effect variegation.’

First established in Drosophila, this phenomenon has now been observed in many eukaryotes, including yeasts, plants, and humans.

5.11: Position-effect Variegation

In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.

Difference between euchromatin and heterochromatin

Euchromatin is a lightly stained, gene-rich, and loosely-bound chromatin region. It is usually dispersed in the nucleus. The histones of euchromatin are extensively acetylated, which allows loose chromatin compaction.

In contrast, heterochromatin is a darkly stained, repeat-rich, gene-poor, and compact chromatin. It is mostly seen at the nuclear periphery, often as clumps. The histones of heterochromatin are methylated, which enables a compact chromatin structure.

Position-effect variegation

Chromosomal rearrangements may position euchromatin genes next to heterochromatin. Such gene rearrangements can result in gene silencing by virtue of being placed near heterochromatin, rather than a change in the gene itself. This phenomenon is called "position-effect variegation (PEV)." Hence, the juxtaposed gene becomes silent in some cells where it is normally active, resulting in a variegated phenotype. The phenomenon of PEV is well studied in Drosophila.

The formation of heterochromatin depends on the histone H3 methylation followed by the association with nonhistone proteins such as Heterochromatin Protein 1 or HP1. Usually, heterochromatin and euchromatin are separated by a buffer region with many repeat-rich regions. PEV indicates that heterochromatin, once formed, can spread beyond the buffer region into the adjoining chromatin. In humans, HUSH complex methylates histones and contributes to the spreading of heterochromatin and hence, position effect variegation.

Suggested Reading

Tags

Position-effect Variegation Eukaryotic Cell DNA Proteins Chromatin Heterochromatin Euchromatin Barrier DNA Sequences Gene Expression Patterns DNA Rearrangement Events Transposition Silenced Genes Inactivated Genes Drosophila White Gene Red Eye Color

X

Simple Hit Counter