DNA methylation is heritable
De novo methylation = new methylation. After replication, the dsDNA is hemi methylated.
recognized and fully methylated made. = maintenance methylation.
15.4 The encode project
The goal is to identify elements that are involved in gene regulation. They do this by mapping
methylation sites, identifying histone sites etc.
15.5 Regulation of translation
How the process of mRNA translation may be regulated by RNA-binding proteins that prevent
ribosomes from initiating translation or affect mRNA degrading
Iron-response element regulates translation and mRNA degradation
Ingested iron binds to transferrin carries iron in the blood recognized by receprot on cell
surface transported into cytosol by endocytosis iron is released, it may be used ore stored in
ferritin. The mRNAs encoding ferritin and transferrin receptor are influenced by IRP. Binds to IRE
within these two mRNAs.
Ferritin mRNA has IRE in 5’ UTR. Iron low IRP binds to IRE and complex prevents translation of
ferritin. Iron high binds to IRP causes IRP not binding to IRE more mRNA production.
Transferrin mRNA 3’ UTR has IRE. IRP binds to IRE, no inhibit, prevent degrading by blocking
action endonuclease. Iron low, mRNA translated, promotes uptake. Iron is abundant iron binds to
IRP IRP dissociates from receptor and mRNA is degraded because endonuclease recognizes sites.
Decrease in transferrin receptor prevent too much uptake
Chapter 16 Gene regulation in Eukaryotes 2
16.1 Overview of epigenetics
An epigentic event must start with a initial event that changes gene expression (methylation), This
change must be passed on to other cells and must not involve a change in sequence. Epigenetics =
study of mechanisms that leas to changes in gene expression, it can be passed on form cell to cell
and is reversible.
Different types of molecular changes underlie epigenetic gene regulation
DNA methylation, chromatin remodeling, covalent histone modification, localization of histone
variants and feedback loops.
Epigenetic changes may be targeted to specific genes by TS or Non-
coding RNAs
Sometimes TSs may bind to specific gene and initiate events that lead to epigenetic changes. Enzyme
like histone-modifiers and DNA methyl-transferase are recruited. Sometimes ncRNAs will do this.
Epigenetic changes may be maintained by cis- or trans-epigenetic
mechanisms
Cis-epigenetic mechanisms = the change is maintained at only 1 site. (genomic imprinting etc.) Trans-
epigenetic mechanisms = change is established by gene that encodes TS, it stimulates its own
expression, feedback loop. The two can experimentally be distinguished by fusing two cells. Cis
, changes will stay on only 1 chromosome, the trans change will also activate the second one, pattern
stays the same during cell division.
Epigenetic gen regulation may occur as programmed developmental
change/be caused by environmental agents
Many epigenetic modification occur at specific stages in the development, for example during cell
differentiation. Environmental agents can also have an effect. Temperature effects vernalization
covalent histone modifications. Diet is an important factor in bees, to make difference between
workers an queens. Toxins like smoke may also effect DNA methylation.
16.2 Heterochromatin: function, structure, formation and
maintenance
Euchromatin usually lies in the center of the nucleus, heterochromatin along the periphery and
attached to the lamina.
Heterochromatin formation plays different functional roles in eukaryotic
cells
Gene silencing = Compact structure inhibits binding of proteins and recruitment GTS
Prevention transposable element movement = random insertion is likely to inactivate a gene,
to minimize this the TE sites are converted to heterochromatin
Prevention of viral proliferation = converting region with proviral DNA into heterochromatin
Constitutive/facultative heterochromatin differ in chromosomal locus and
molecular features
Constitutive heterochromatin :
Chromosomal locations = closer to centromere (pericentric region) an telomeres
Repeat sequences = lots of tandem repeats, satellite sequences which help the compaction
DNA methylation = highly methylated in vertebrates and plants
Histone modifications = trimethylation of lysine at 9 th position on H3. Consequences of
PTMs: Proteins bind to PTMs via reader domains, (writer domains = catalyze addition PTM,
eraser domain = remove PTM) Bind to chromatin-modifying enzymes and recruit them for
chromatin remodeling
Facultative heterochromatin:
Chromosomal locations = between centromeres and telemores where there a genes
Repeat sequences = in animals, LINE-type repeated sequences
DNA methylation = in CpG islands in regulatory regions
Histone modifications = The H2K9me3 and often H2K27me3 associated with hetero
chromatin formation that silences genes
The pattern of heterochromatin in given chromosome is passed from cell
to cell
During the M phase the chromatin is condensed. The resulting two daughter cells will retain the
same pattern of constitutive and facultative heterochromatin as the mother cell.
Series molecular events result in gene silencing and produces
heterochromatin with higher-order structure
Higher-order structure = assemblage of nucleosomes that assumes reproducible conformation in 3D.
Heterochromatin formation is thought to involve: PTM of histones, binding proteins to nucleosomes,
chromatin remodeling, DNA methylation, binding ncRNAs. Some silence gene expression, other
promote formation of higher-order structures:
De novo methylation = new methylation. After replication, the dsDNA is hemi methylated.
recognized and fully methylated made. = maintenance methylation.
15.4 The encode project
The goal is to identify elements that are involved in gene regulation. They do this by mapping
methylation sites, identifying histone sites etc.
15.5 Regulation of translation
How the process of mRNA translation may be regulated by RNA-binding proteins that prevent
ribosomes from initiating translation or affect mRNA degrading
Iron-response element regulates translation and mRNA degradation
Ingested iron binds to transferrin carries iron in the blood recognized by receprot on cell
surface transported into cytosol by endocytosis iron is released, it may be used ore stored in
ferritin. The mRNAs encoding ferritin and transferrin receptor are influenced by IRP. Binds to IRE
within these two mRNAs.
Ferritin mRNA has IRE in 5’ UTR. Iron low IRP binds to IRE and complex prevents translation of
ferritin. Iron high binds to IRP causes IRP not binding to IRE more mRNA production.
Transferrin mRNA 3’ UTR has IRE. IRP binds to IRE, no inhibit, prevent degrading by blocking
action endonuclease. Iron low, mRNA translated, promotes uptake. Iron is abundant iron binds to
IRP IRP dissociates from receptor and mRNA is degraded because endonuclease recognizes sites.
Decrease in transferrin receptor prevent too much uptake
Chapter 16 Gene regulation in Eukaryotes 2
16.1 Overview of epigenetics
An epigentic event must start with a initial event that changes gene expression (methylation), This
change must be passed on to other cells and must not involve a change in sequence. Epigenetics =
study of mechanisms that leas to changes in gene expression, it can be passed on form cell to cell
and is reversible.
Different types of molecular changes underlie epigenetic gene regulation
DNA methylation, chromatin remodeling, covalent histone modification, localization of histone
variants and feedback loops.
Epigenetic changes may be targeted to specific genes by TS or Non-
coding RNAs
Sometimes TSs may bind to specific gene and initiate events that lead to epigenetic changes. Enzyme
like histone-modifiers and DNA methyl-transferase are recruited. Sometimes ncRNAs will do this.
Epigenetic changes may be maintained by cis- or trans-epigenetic
mechanisms
Cis-epigenetic mechanisms = the change is maintained at only 1 site. (genomic imprinting etc.) Trans-
epigenetic mechanisms = change is established by gene that encodes TS, it stimulates its own
expression, feedback loop. The two can experimentally be distinguished by fusing two cells. Cis
, changes will stay on only 1 chromosome, the trans change will also activate the second one, pattern
stays the same during cell division.
Epigenetic gen regulation may occur as programmed developmental
change/be caused by environmental agents
Many epigenetic modification occur at specific stages in the development, for example during cell
differentiation. Environmental agents can also have an effect. Temperature effects vernalization
covalent histone modifications. Diet is an important factor in bees, to make difference between
workers an queens. Toxins like smoke may also effect DNA methylation.
16.2 Heterochromatin: function, structure, formation and
maintenance
Euchromatin usually lies in the center of the nucleus, heterochromatin along the periphery and
attached to the lamina.
Heterochromatin formation plays different functional roles in eukaryotic
cells
Gene silencing = Compact structure inhibits binding of proteins and recruitment GTS
Prevention transposable element movement = random insertion is likely to inactivate a gene,
to minimize this the TE sites are converted to heterochromatin
Prevention of viral proliferation = converting region with proviral DNA into heterochromatin
Constitutive/facultative heterochromatin differ in chromosomal locus and
molecular features
Constitutive heterochromatin :
Chromosomal locations = closer to centromere (pericentric region) an telomeres
Repeat sequences = lots of tandem repeats, satellite sequences which help the compaction
DNA methylation = highly methylated in vertebrates and plants
Histone modifications = trimethylation of lysine at 9 th position on H3. Consequences of
PTMs: Proteins bind to PTMs via reader domains, (writer domains = catalyze addition PTM,
eraser domain = remove PTM) Bind to chromatin-modifying enzymes and recruit them for
chromatin remodeling
Facultative heterochromatin:
Chromosomal locations = between centromeres and telemores where there a genes
Repeat sequences = in animals, LINE-type repeated sequences
DNA methylation = in CpG islands in regulatory regions
Histone modifications = The H2K9me3 and often H2K27me3 associated with hetero
chromatin formation that silences genes
The pattern of heterochromatin in given chromosome is passed from cell
to cell
During the M phase the chromatin is condensed. The resulting two daughter cells will retain the
same pattern of constitutive and facultative heterochromatin as the mother cell.
Series molecular events result in gene silencing and produces
heterochromatin with higher-order structure
Higher-order structure = assemblage of nucleosomes that assumes reproducible conformation in 3D.
Heterochromatin formation is thought to involve: PTM of histones, binding proteins to nucleosomes,
chromatin remodeling, DNA methylation, binding ncRNAs. Some silence gene expression, other
promote formation of higher-order structures:
