Current Opinion in Genetics & Development,
Год журнала:
2024,
Номер
86, С. 102201 - 102201
Опубликована: Май 2, 2024
Polycomb-associated
chromatin
and
pericentromeric
heterochromatin
form
genomic
domains
important
for
the
epigenetic
regulation
of
gene
expression.
Both
Polycomb
complexes
factors
rely
on
'read
write'
mechanisms,
which,
their
own,
are
not
sufficient
to
explain
formation
maintenance
these
domains.
Microscopy
has
revealed
that
they
specific
nuclear
compartments
separated
from
rest
genome.
Recently,
some
subunits
molecular
machineries
have
been
shown
undergo
phase
separation,
both
in
vitro
vivo,
suggesting
separation
might
play
roles
function
two
kinds
repressive
chromatin.
In
this
review,
we
will
present
recent
advances
field
facultative
constitutive
through
separation.
The EMBO Journal,
Год журнала:
2024,
Номер
43(13), С. 2685 - 2714
Опубликована: Июнь 3, 2024
Abstract
Constitutive
heterochromatin
is
essential
for
transcriptional
silencing
and
genome
integrity.
The
establishment
of
constitutive
in
early
embryos
its
role
fruitfly
development
are
unknown.
Lysine
9
trimethylation
histone
H3
(H3K9me3)
recruitment
epigenetic
reader,
protein
1a
(HP1a),
hallmarks
heterochromatin.
Here,
we
show
that
H3K9me3
transmitted
from
the
maternal
germline
to
next
generation.
Maternally
inherited
H3K9me3,
methyltransferases
(HMT)
depositing
it,
required
organization
heterochromatin:
lacking
H3K9
methylation
display
de-condensation
pericentromeric
regions,
centromere-centromere
de-clustering,
mitotic
defects,
nuclear
shape
irregularities,
resulting
embryo
lethality.
Unexpectedly,
quantitative
CUT&Tag
4D
microscopy
measurements
HP1a
coupled
with
biophysical
modeling
revealed
H3K9me2/3
largely
dispensable
recruitment.
Instead,
main
function
at
this
developmental
stage
drive
clustering
subsequent
compaction.
Our
results
binding
absence
not
sufficient
promote
proper
formation.
loss
HMTs
alters
hinders
embryonic
development.
ABSTRACT
We
propose
that
several
chromatin-mediated
regulatory
processes
are
dominated
by
source-sink
relationships
in
which
factors
operate
as
‘sources’
to
produce
or
provide
a
resource
and
compete
with
each
other
occupy
separate
‘sinks’.
In
this
model,
large
portions
of
genomic
DNA
‘sinks’,
filled
‘sources’,
such
available
histone
variants,
covalent
modifications
histones,
the
readers
these
non-coding
RNAs.
Competing
occupation
for
sinks
different
sources
leads
distinct
states
equilibrium
differentiated
cells.
During
dynamic
developmental
events,
sexual
reproduction,
we
dramatic
rapid
reconfiguration
modifies
chromatin
states.
envision
re-routing
could
occur
altering
dimensions
sink,
existing
sink
varying
size
source,
providing
central
mechanism
explain
plethora
epigenetic
phenomena,
contribute
phenotypic
variegation,
zygotic
genome
activation
nucleolar
dominance.
Histone
H3
lysine-9
methylation
(H3K9me)
is
a
hallmark
of
the
condensed
and
transcriptionally
silent
heterochromatin.
It
remains
unclear
how
H3K9me
controls
transcription
silencing
cells
delimit
domains
to
avoid
essential
genes.
Here,
using
Journal of the American Chemical Society,
Год журнала:
2023,
Номер
145(44), С. 23994 - 24004
Опубликована: Окт. 23, 2023
In
the
nucleus,
transcriptionally
silent
genes
are
sequestered
into
heterochromatin
compartments
comprising
nucleosomes
decorated
with
histone
H3
Lys9
trimethylation
and
a
protein
called
HP1α.
This
can
form
liquid–liquid
droplets
in
vitro
potentially
organize
through
phase
separation
mechanism
that
is
promoted
by
phosphorylation.
Elucidating
molecular
interactions
drive
HP1α
its
consequences
on
nucleosome
structure
dynamics
has
been
challenging
due
to
viscous
heterogeneous
nature
of
such
assemblies.
Here,
we
tackle
this
problem
combination
solution
solid-state
NMR
spectroscopy,
which
allows
us
dissect
phosphorylated
context
separation.
Our
experiments
indicate
human
does
not
cause
any
major
rearrangements
core,
contrast
yeast
homologue
Swi6.
Instead,
interacts
specifically
methylated
tails
slows
H4
tails.
results
shed
light
how
proteins
may
regulate
landscape,
while
our
approach
provides
an
atomic
resolution
view
dynamic
biological
system
regulated
complex
network
post-translational
modifications.
Current Opinion in Genetics & Development,
Год журнала:
2024,
Номер
86, С. 102201 - 102201
Опубликована: Май 2, 2024
Polycomb-associated
chromatin
and
pericentromeric
heterochromatin
form
genomic
domains
important
for
the
epigenetic
regulation
of
gene
expression.
Both
Polycomb
complexes
factors
rely
on
'read
write'
mechanisms,
which,
their
own,
are
not
sufficient
to
explain
formation
maintenance
these
domains.
Microscopy
has
revealed
that
they
specific
nuclear
compartments
separated
from
rest
genome.
Recently,
some
subunits
molecular
machineries
have
been
shown
undergo
phase
separation,
both
in
vitro
vivo,
suggesting
separation
might
play
roles
function
two
kinds
repressive
chromatin.
In
this
review,
we
will
present
recent
advances
field
facultative
constitutive
through
separation.
