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Genetics summary chapter 16 VU amsterdam
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This summary covers complete chapter 16 of genetics at the Vrije Universiteit Amsterdam.
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Chapter 16Epigenetics – the study of mechanisms that lead to changes in gene expression that can be passed from cell to cell and are
reversible, but do not involve a change in the DNA sequence – explores changes in gene expression that be permanent over
the course of an individual’s life, but is not permanent over the course of multiple generations. An epigenetic effect begins
with an initial event that causes a change in gene expression. The change must be passed from cell to cell and does not
involve a change in DNA sequence. Thus, a key feature of epigenetic effect is the long-term maintenance of a change in
gene expression. A gene that may be silenced in an individual, may be active in the offspring of that individual.
- Epimutation: an heritable change in gene expression that does not alter the DNA sequence. In multicellular
species that reproduce via gametes (sperm/egg cells), when an epigenetic change is passed from parent to
offspring epigenetic inheritance/ transgenerational epigenetic inheritance. An example is genomic imprinting.
The most common types of molecular changes that underlie epigenetic control are:
- DNA methylation: methyl groups may be attached to cytosine bases in DNA. When methylation occurs near
promotors, transcription is inhibited.
- Chromatin remodeling: nucleosomes may be moved/removed. When such changes occur in the vicinity of the
promotor, the level of transcription is altered. Also, larger-scale changes in chromatin structure may occur, such
as those that happen during X-chromosome inactivation of female mammals.
- Covalent histone modification: specific amino acid side chains found on the amino-terminal tails of histones can
be modified. They can be acylated, phosphorylated, methylated.
- Histone variants: histone variants may become localized to specific positions, such as near the promoters and
affect transcription.
- Feedback loops: the activation of a gene that encodes a regulatory transcription factor may result in a feedback
loop in which the transcription factor continues to stimulate its own expression.
These types of changes may also be involved non epigenetic gene regulation. In some cases, regulatory transcription factors
may bind to a specific gene and initiate a series of events that leads to epigenetic modification. For this to occur, the
regulatory transcription factor recognizes specific sites in the genome and recruit proteins, such as histone-modifying
enzymes and DNA methyltransferase, to those sites. This recruitment leads to epigenetic changes.
In other cases, non-coding RNAs (ncRNAs) – RNAs that do not encode polypeptides – bind to specific gene sequences
instead of the transcription factors. They recruit other proteins and this leads to changes in the expression of the gene. The
types of epigenetic changes (DNA methylation, etc.) can be maintained in two general ways:
1. Cis-epigenetic mechanism: the epigenetic change at a given site is maintained only at that site; it does not effect
the expression of the same gene located elsewhere in the cell nucleus. Examples: genomic imprinting and X-
inactivation.
2. Trans-epigenetic mechanism: occurs via diffusible molecules, such as proteins/ncRNAs. An epigenetic change is
established by activating the gene that encodes a regulatory transcription factor. After the transcription factor is
made, it stimulates its own expression. If the gene of this transcription factor is present in two copies in the cell,
both copies will be activated because the transcription factor is a diffusible protein and many of these proteins
are made when the gene is expressed. This pattern in which both copies of a gene are activated will be
maintained during cell division. The transcription factor may also turn other gene son in the cell that encodes
proteins that effect cell structure and function a trans-epigenetic mechanism will have a phenotypic effect.
This type is more commonly found in prokaryotes and single-celled (haploid) eukaryotes. Examples: feedback
loops and paramutation.
Cis- and trans-epigenetic mechanisms can be researched through cell-fusion experiments. If the cells are fused, two
different outcomes are possible. If cis-epigenetic mechanism is involved, the epigenetic modification will be maintained for
one copy of the gene. The other copy will not be altered. If it’s the case with a trans-epigenetic mechanism, both copies of
the gene will be expressed/modified, because the fused cell will contain enough transcription factor protein to stimulate
both copies.
Epigenetic gene regulation may occur as a programmed development change or be caused by environmental agents.
Environmentally induced changes in organism’s characteristics are rooted in epigenetic changes that alter gene expression.
1. Temperature changes have epigenetic effects. Vernalization – certain plants need a colder temperature during in
spring – involves covalent histone modifications of specific genes, which persist from winter to spring.
2. Diet: there are queen bees and worker bees. Only larvae that are fed royal jelly develop into queen bees the
body types are different due to dietary differences. DNA methylation is different in both bees and this pattern of
methylation affects the expression of genes.
3. Toxins: exposure to tobacco in humans alters DNA methylation and covalent histone modification of specific
genes in the lung cells cancer.
Chromosomal DNA is packaged in the cell nucleus by the formation of chromatin (nucleosomes are the basic repeating
units). Chromatin does not only contain DNA and proteins, but also ncRNAs. Chromatin occurs in two general ways:
, Chapter 16
1. Euchromatin: loosely packed DNA. Chromosomes are composed of regions thar are not stained during
interphase. Occupies a central position.
2. Heterochromatin: tightly packed DNA. Chromosomes are composed of regions that stay stained during
interphase. It has an inhibitory effect on gene expression. Mostly localized along the periphery of the cell nucleus
and is attached to the nuclear lamina that lines the inner nuclear membrane. They both have different nuclear
domains.
The formation of heterochromatin plays a key role in eukaryotic cells:
- Gene silencing: heterochromatin formation is associated with inhibiting transcription. Because of the more
compact structure of heterochromatin, the formation silences the expression of the genes by limiting access to
DNA of DNA-binding-proteins such as activators. In other cases, it may inhibit the recruitment of general
transcription factors/coactivators.
- Preventing of transposable element movement: TEs are mobile DNA segments that can insert themselves into
multiple sites within a genome. The random insertion of a TE into a gene is likely to inactivate the gene’s function.
Therefore, transposition can have a negative effect of gene expression, which may be detrimental to cell structure
and function. The sites where the TEs are located are converted to heterochromatin, which silences genes that
are needed for the transposition process.
- Preventing of viral proliferation: another role of heterochromatin formation is to prevent proliferation of viruses.
Some viruses integrate their DNA into the host genome in the form of a provirus. One way to prevent the provirus
from becoming active and producing new viruses is to convert the region containing proviral DNA into
heterochromatin, thereby inhibiting the expression of viral genes that are needed to produce new viruses.
Some regions of heterochromatin are stained only in certain cells facultative heterochromatin. In facultative
heterochromatin, you often go from euchromatin heterochromatin or from heterochromatin euchromatin.
Heterochromatin regions that are stained in all cell types constitutive heterochromatin.
Constitutive heterochromatin- has consistent features with regard Facultative heterochromatin – the formation of the facultative
to DNA sequencing, DNA modifications and histone modifications heterochromatin is reversible. Its heterochromatic state depends on the
yeast and mammalian cells. stage of development of the cell type. It plays a role in processes such as
genomic imprinting, gene silencing and X-chromosome inactivation. .
Chromosomal locations: they tend to be located close to a Chromosomal locations: they may occur at multiple discrete sites that are
centromere (pericentric region) and also at telomeres. These regions located between the centromeres and telomeres. These regions contain
carry a few genes. many genes.
Repeat sequences: the DNA within constitutive heterochromatin is Repeat sequence: in animals, the DNA is of F.H is characterized by the
composed of short, tandemly repeated sequences satellite presence if LINE-type repeated sequences. These sequences, dispersed
sequences (because they sediment away from the rest of the throughout the genome, may initiate the propagation of a condensed
chromosomal DNA. These satellite DNA sequences are able to fold chromatin structure.
themselves and may have an important role in the formation of
highly compact structures.
DNA methylation: it is highly methylated on cytosines. DNA methylation: is more discrete than in C.H and often occurs in CpG
islands, which are located in the regulatory regions of genes.
Histone modifications: the tri-methylation of lysine at the 9th Histone modification: H3K9me3 is also found in F.H. They also have tri-
position in histone H3 (H3K9me3) in yeast and animal cells. A di- methylation of the 27th lysine of histone H3. This post-translation
methylation (H3K9me2) in plants. modification is associated with heterochromatin formation that silences
genes in a cell-specific manner.
The consequences of these posttranslational modifications (PTMs) such as H3K9me3 is that some proteins bind to
nucleosomes via protein domains called reader domains can be found in the same proteins that also contain domains
that modify chromatin. These domains are called writer domains if they catalyse the addition of PTMS, or eraser domains if
they remove PTMs. Proteins with reader domains may bind to chromatin-modifying enzymes or chromatin-remodeling
complexes and thereby recruit them to a nucleosome via the recruitment domain in the reader domain (see 402). This
recruitment leads to PTMS and chromatin remodeling that contribute to the formation of heterochromatin.
Much of the interphase chromosome is composed of euchromatin, in which most genes are not silenced. During the M
phase of mitosis, these euchromatic regions condense. Follow the M phase, in interphase in the resulting two daughter
cells, the chromosome will usually retain the same pattern of constitutive and facultative heterochromatin that was found
in the mother cell. A series of molecular events results in gene silencing and produces heterochromatin with a higher-order
structure used to describe the assemblage of nucleosomes that assumes a reproducible conformation in 3D space. The
30 nm-fiber is a higher-order structure found in euchromatin. Heterochromatin formation is thought to be involved in the
following:
- Posttranslational modifications in histones,
- Binding of proteins to nucleosomes,
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