In
yeast
and
humans,
previous
experiences
can
lead
to
epigenetic
transcriptional
memory:
repressed
genes
that
exhibit
mitotically
heritable
changes
in
chromatin
structure
promoter
recruitment
of
poised
RNA
polymerase
II
preinitiation
complex
(RNAPII
PIC),
which
enhances
future
reactivation.
Here,
we
show
INO1
memory
is
initiated
by
binding
the
Sfl1
transcription
factor
cis-acting
Memory
Recruitment
Sequence,
targeting
nuclear
periphery.
requires
a
remodeled
form
Set1/COMPASS
methyltransferase
lacking
Spp1,
dimethylates
histone
H3
lysine
4
(H3K4me2).
H3K4me2
recruits
SET3C
complex,
plays
an
essential
role
maintaining
this
mark.
Finally,
while
active
associated
with
Cdk8-
Mediator,
during
memory,
Cdk8+
Mediator
RNAPII
PIC
Kin28
CTD
kinase.
Aspects
mechanism
are
generalizable
conserved
human
cells.
Thus,
COMPASS
repurposed
promote
poising
highly
mechanism.
Epigenetic
regulation
of
gene
expression
in
metazoans
is
central
for
establishing
cellular
diversity,
and
its
deregulation
can
result
pathological
conditions.
Although
transcription
factors
are
essential
implementing
programs,
they
do
not
function
isolation
require
the
recruitment
various
chromatin-modifying
-remodeling
machineries.
A
classic
example
developmental
chromatin
balanced
activities
Polycomb
group
(PcG)
proteins
within
PRC1
PRC2
complexes,
Trithorax
(TrxG)
COMPASS
family,
which
highly
mutated
a
large
number
human
diseases.
In
this
review,
we
will
discuss
latest
findings
regarding
properties
PcG
families
insight
provide
into
epigenetic
control
under
physiological
settings.
Abstract
The
epigenetic
modifications
of
histones
are
versatile
marks
that
intimately
connected
to
development
and
disease
pathogenesis
including
human
cancers.
In
this
review,
we
will
discuss
the
many
different
types
histone
biological
processes
with
which
they
involved.
Specifically,
review
enzymatic
machineries
involved
in
cancer
progression,
how
apply
currently
available
small
molecule
inhibitors
for
modifiers
as
tool
compounds
study
functional
significance
their
clinical
implications.
Brain Pathology,
Год журнала:
2015,
Номер
26(5), С. 569 - 580
Опубликована: Окт. 30, 2015
Somatic
mutations
of
the
H3F3A
and
HIST1H3B
genes
encoding
histone
H3
variants,
H3.3
H3.1,
were
recently
identified
in
high-grade
gliomas
arising
thalamus,
pons
spinal
cord
children
young
adults.
However,
complete
range
patients
locations
which
these
tumors
arise,
as
well
morphologic
spectrum
associated
genetic
alterations
remain
undefined.
Here,
we
describe
a
series
47
diffuse
midline
with
H3-K27M
mutation.
The
25
male
22
female
ranged
age
from
2
to
65
years
(median
=
14).
Tumors
centered
not
only
pons,
cord,
but
also
third
ventricle,
hypothalamus,
pineal
region
cerebellum.
Patients
pontine
younger
7
years)
than
those
thalamic
24
or
tumors.
A
wide
was
encountered
including
giant
cells,
epithelioid
rhabdoid
primitive
neuroectodermal
tumor
(PNET)-like
foci,
neuropil-like
islands,
pilomyxoid
features,
ependymal-like
areas,
sarcomatous
transformation,
ganglionic
differentiation
pleomorphic
xanthoastrocytoma
(PXA)-like
areas.
In
this
series,
mutation
mutually
exclusive
IDH1
EGFR
amplification,
rarely
co-occurred
BRAF-V600E
mutation,
commonly
p53
overexpression,
ATRX
loss
(except
gliomas),
monosomy
10.
Science,
Год журнала:
2016,
Номер
352(6287), С. 844 - 849
Опубликована: Май 12, 2016
An
oncohistone
deranges
inhibitory
chromatin
Missense
mutations
(that
change
one
amino
acid
for
another)
in
histone
H3
can
produce
a
so-called
and
are
found
number
of
pediatric
cancers.
For
example,
the
lysine-36–to-methionine
(K36M)
mutation
is
seen
almost
all
chondroblastomas.
Lu
et
al.
show
that
K36M
mutant
histones
oncogenic,
they
inhibit
normal
methylation
this
same
residue
wild-type
histones.
The
also
interfere
with
development
bone-related
cells
deposition
marks.
Science
,
issue
p.
844
The
Polycomb
group
(PcG)
of
proteins
defines
a
subset
factors
that
physically
associate
and
function
to
maintain
the
positional
identity
cells
from
embryo
adult
stages.
PcG
has
long
been
considered
paradigmatic
model
for
epigenetic
maintenance
gene
transcription
programs.
Despite
intensive
research
efforts
unveil
molecular
mechanisms
action
proteins,
several
fundamental
questions
remain
unresolved:
How
many
different
complexes
exist
in
mammalian
cells?
are
targeted
specific
loci?
does
regulate
transcription?
In
this
review,
we
discuss
diversity
cells,
examine
newly
identified
modes
recruitment
chromatin,
highlight
latest
insights
into
underlying
PcGs
regulation
three-dimensional
chromatin
conformation.
