Chromatin structure and control of gene transcription
Description
Undergraduate BMS238 Cell and molecular biology (Chromosomes) Mind Map on Chromatin structure and control of gene transcription, created by Kristi Brogden on 08/16/2014.
Thus: different Histone
modifications are distinct
elements of a transcriptional
regulatory code
an epigenetic code that lies on
top of the genetic code
governs when and where genetic
information is expressed
The Polycomb Group of proteins (Polycomb
Repressive Complexes; PRC) includes proteins
that can generate or recognise repressive
chromatin modifications – Histone Code Writers
and Readers
Combinations of different Histone modifications may
be “read” by different Histone Code Reader proteins
Histone Code Readers allow
information integration that
determines whether a gene is
ON or OFF
Histone Code Readers
and Code Writers can
recruit each other!
these interactions can help
to spread the histone code
with impacts on gene expression
A close functional relationship exists between DNA
methylation and transcriptionally repressive histone
methylation
Transcriptionally inactive promoters are
frequently rich in methylated CpG dinucleotides
Addition of methyl groups to cytosine
residues is mediated by DNA
methyltransferases (DNMTs)
The histone methyltransferase EZH2 (methylates H3
on K27) physically interacts with DNMTs and together
these enzymes mutually reinforce each other’s effects
Genetic changes
Genetic alterations to DNA sequence
can permanently affect gene expression
epigenetic changes to chromatin structure,
although relatively stable, are reversible
Epigenetic modifications facilitate stable changes to gene
expression, which may persist for the life of a cell or
organism, but they can be erased in the germ line
How do transcription activator proteins work?
Activator proteins typically induce combinations of these effects
How do transcription repressor proteins work?
X chromosome
Mammalian X-chromosome
Inactivation equalizes the levels of
X-chromosome derived gene
products in males and females
One X chromosome copy is silenced in each somatic cell
during early development of female embryo, i.e. Xp or Xm
Initial selection of the
chromosome for
silencing is random
The silencing decision is then propagated clonally i.e. all
progeny of each cell in which the silencing decision was
taken inherit the same silenced X chromosome, i.e. Xp or Xm
Males, XY: 1 dose of X-linked genes
Females, XX: 2 doses of X-linked genes
X-chromosome inactivation:
the case of the calico cat
XO orange allele
Xo black allele
Males:
XO Y:
orange
Xo Y:
black
Females:
XO XO
: orange
Xo Xo:
black
XO Xo:
calico
Calico cats are
exclusively
female
Calico cats are
heterozygous for a
mutation in an X-linked
coat pigment gene
Face, neck, belly
and feet are white
because no pigment
cells in these areas
Patches of orange and black
because of random X-inactivation
during early embryogenesis
Mechanism of X-inactivation
involves synthesis of a non-coding RNA
(Xist) from the X-inactivation centre (XIC) on
the chromosome destined for inactivation
Xist RNA binds to the X chromosome in cis and promotes chromatin
condensation via a process that spreads away from from the XIC in
both directions
Xist RNA promotes the formation of silent chromatin by
recruiting histone modifying enzymes and other Polycomb
Group components, leading to the H3K27 and H3K9
methylation of core Histones in X chromosome chromatin
The Polycomb proteins - Histone Code Writers and Readers –
detect Xist transcripts on the X chromosome that is to be
inactivated and cause its transcriptional silencing
The Barr Body
a highly condensed inactive X
chromosome at the periphery of the
nucleus of female somatic cells
A limiting amount of an unknown
autosomal activator is thought to
maintain expression of the active X
Euchromatin and heterochromatin
Euchromatin
contains transcriptionally
active genes (and genes
that are competent for
transcriptional activation)
Heterochromatin
contains
transcriptionally silent
genes and repetitive
DNA sequences.
two functionally distinct types of
chromatin in eukaryotic cells
Position effects
Abnormal rearrangments of euchromatin and
heterochromatin cause Position Effects that affect
the transcriptional activity of the euchromatic genes.
Aberrant chromosomal rearrangements that
place heterochromatin next to euchromatin
can shut down euchromatic gene activity
Chromosomal rearrangements that alter the
chromatin environment around the White
locus in Drosophila cause Position Effects,
which influence eye pigmentation
The transcription silencing property of
heterochromatin spreads into euchromatin
and shuts down euchromatic genes
but not completely:
Position Effect Variegation
of gene expression
occurs in all eukaryotes
reflects an intersection between genetics
(mutation) and epigenetics (effects of
chromatin structure on transcription)