Chapter 15 Chapter 15 considered two general aspects of eukaryotic gene regulation
1. Regulatory transcription factors may activate or inhibit genes
2. Changes in chromatin structure affect gene expression:
Histone modifications
Histone variants
Nucleosome position changes
DNA ‘modification’ (cytosine methylation)
Changes mentioned under 2 are called Epigenetic regulation
Epigenetics is 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 sequence of DNA > Involves changes in Chromatin
structure and DNA methylation patterns.
Epigenetic inheritance involves epigenetic changes that
are passed from cell to cell, and in some case from parent
to offspring (transgenerational epigenetic inheritance); An
example is genomic imprinting.
Different types of molecular change underlie epigenetic
regulation
DNA methylation
Chromatin remodeling
Covalent histone modification
Localization of histone variants
Feedback loops
epimutation = heritable change in gene expression that
does not alter DNA sequence
Epigenetic changes may be
targeted to genes by
transcription factors or by
noncoding RNAs
Cis- and trans Epigenetic changes may occur in cis or trans
epigenetic Cis-epigenetic changes are maintained at a specific site (DNA sequence). For example, a cis-
changes epigenetic change may affect only one copy of gene but not the other copy. These changes are
maintained during cell division and passed on to daughter cells.
Trans-epigenetic changes are maintained by diffusible factors, such as transcription factors. A
trans-epigenetic change affects both copies of a gene.
Cis- and trans-epigenetic changes can be distinguished via cell fusion.
, Two general • Epigenetic gene regulation may occur as a programmed developmental change
categories of – Genomic imprinting
epigenetic gene – X chromosome inactivation
regulation – Cell differentiation
• Epigenetic changes may be caused by environmental agents
– Temperature
– Diet
– Toxins
heterochromatin Function, structure, formation, maintenance
Chromosomal DNA in eukaryotic cell is packaged into chromatin. Nucleosomes are the basic unit. 147 bp
of DNA wrapped around an octamer of histone proteins (H2A, H2B, H3, and H4). Chromatin composed
of DNA, protein, non-coding RNAs
• Euchromatin – regions that are not stained during interphase. Transcriptionally active. Occupies
a central position in the nucleus.
• Heterochromatin – regions that are stained throughout the cell cycle. Greater level of
compaction. Inhibitory effect on gene expression. Localized along the periphery of the nucleus;
attached to nuclear lamina.
Roles of • Gene silencing – inhibition of transcription; may limit access of activators or inhibit other aspects
heterochromatin of transcription
• Prevention of transposable element movement – genes needed for transposition are silenced
• Prevention of viral proliferation – genes needed to produce more viruses are silenced
Constitutive vs Constitutive heterochromatin – heterochromatic at the same location in all cell types
facultative Facultative heterochromatin – locations vary among different cell types. Allows silencing of genes in a
cell specific manner
Constitutive Characteristics
• Chromosomal location – close to centromere or
telomere
• Repeat sequences – generally composed of many
short tandemly repeated sequences
• DNA methylation – highly methylated on cytosines
in vertebrates and plants
• Histone modifications – H3K9me3 (PMT;
methylation of a lysine at the ninth position in
histone H3) common in constitutive
heterochromatin in yeast and animals;
You are studying a chromosome in a new animal species.
The presence of what element would make you most
confident that a region is facultative heterochromatin and
not constitutive heterochromatin? LINE-type repeat
sequences .
Posttranslational Amino-terminal tails of histone proteins subject to different posttranslational modifications (PTMs).
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