Heterochromatin, epigenetics and gene expression

Published on February 4, 2014   51 min

Other Talks in the Series: Epigenetics, Chromatin, Transcription and Cancer

Other Talks in the Series: Molecular Genetics of Human Disease

The title of this talk is Heterochromatin, Epigenetics and Gene Expression. I'm Joel Eissenberg. I'm a professor in the Department of Biochemistry and Molecular Biology at Saint Louis University School of Medicine. My goal in this talk is to survey our understanding of heterochromatin and its connection to the idea of epigenetic control of gene expression. Terms like heterochromatin and epigenetics are frequently used to disguise, rather than explicate, our understanding of how cells organize and use genetic information. In this presentation, I'll define these terms and discuss epigenetics in the context of heterochromatin and the evidence that it can influence gene expression.
The term heterochromatin was coined by Emil Heitz to refer to the material in the eukaryotic nucleus that fails to decondense after telophase in the cell cycle. On the left in this slide is an image showing the chromosomes of a cell at or near telophase stained with a fluorescent dye that labels DNA. The bright fluorescent staining, is coextensive with the chromosomes. In contrast, the interphase nucleus on the right is filled with DNA, but only certain regions stain brightly, the heterochromatin. The condensed state of heterochromatin concentrates the DNA, making these regions stand out on the background of the rest of the DNA fluorescents in the nucleus. This property distinguishes it from the remaining so-called euchromatin, or true chromatin, that undergoes cyclic condensation and decondensation. In contrast, heterochromatin exhibits heterocyclic behavior, hence the term heterochromatin. Thus, the term heterochromatin was originally coined to describe a cytological phenomenon, not a genetic or biochemical phenomenon. Heitz ultimately showed that most or all eukaryotic chromosomes are differentiated along their lengths by zones of euchromatin, which he recognized as relatively gene rich, and heterochromatin, which he recognized as relatively gene poor. More recently, the term heterochromatin has been used more promiscuously to describe any form of chromatin associated with transcriptional silencing and/or chromatin enriched for certain biochemical markers, such as cytosine methylation, or certain histone modifications. In this presentation, I'll stick to examples that are consistent with the original definition of the word.
Upon comparing heterochromatin in different cells from the same organism, two types of heterochromatin may be distinguished. Many heterochromatic regions, such as the regions surrounding each centromere, are heterochromatic in all cell types. This is called constitutive heterochromatin. In contrast to the ever-present nature of constitutive heterochromatin, the term facultative heterochromatin refers to chromosomal regions that may be heterochromatic in some cells and euchromatic in other cell types.
Cell to cell differences in the extent of heterochromatin are evident in the electron micrographs shown here. On the left is the nucleus of a neuron. The dark material in the nucleus is the heterochromatin. Note in particular the amount of heterochromatin that lies just beneath the nuclear membrane. In contrast, note the much thicker layer of heterochromatin that underlies the nuclear membrane of the quiescent lymphocyte, shown on the right. This variation is thought to be a reflection of the higher transcriptional activity of the neuronal nucleus, relative to the more modest overall transcriptional activity, in an unstimulated lymphocyte. The difference is the amount of facultative heterochromatin.
A conspicuous example of facultative heterochromatin, found in the somatic nuclei of all mammalian females, is the Barr body. In humans, one or the other X chromosome is randomly inactivated, early in development. And the inactive X chromosome takes on the condensed, densely stained appearance of heterochromatin, indicated by the arrowhead in this figure. This heterochromatic X chromosome is called the Barr body. The inactivation is clonally inherited. Remarkably, the other X chromosome in the same nucleus escapes this inactivation. In mammalian cells containing more than two X chromosomes, all but one X are inactivated and form Barr bodies. A mechanistic understanding of both the coordinate gene silencing and distinctive condensed appearance of the Barr body is still lacking.
A particularly vivid and useful example of the silencing effects of heterochromatin on euchromatic genes, involves the white gene in Drosophila. The white gene normally resides near the tip of the X chromosome in the fly. Its normal function is to program red eye color in the adult compounded eye. In this cartoon, the euchromatin of the X is represented as a thin line, while the constitutive heterochromatin of the X is shown as rectangles flanking the centromere, which is represented by the oval.

Heterochromatin, epigenetics and gene expression

Embed in course/own notes