Differential
gene
transcription
enables
development
and
homeostasis
in
all
animals
is
regulated
by
two
major
classes
of
distal
cis-regulatory
DNA
elements
(CREs):
enhancers
silencers.
Although
have
been
thoroughly
characterized,
the
properties
mechanisms
silencers
remain
largely
unknown.
By
an
unbiased
genome-wide
functional
screen
Drosophila
melanogaster
S2
cells,
we
discover
a
class
that
bind
one
three
factors
(TFs)
are
generally
not
included
chromatin-defined
CRE
catalogs
as
they
mostly
lack
detectable
accessibility.
The
silencer-binding
TF
CG11247,
which
term
Saft,
safeguards
cell
fate
decisions
vivo
functions
via
highly
conserved
domain
zinc-finger-associated
C-terminal
(ZAC)
corepressor
G9a,
independently
G9a's
H3K9-methyltransferase
activity.
Overall,
our
identification
with
unexpected
has
important
implications
for
understanding
future
study
repressive
CREs,
well
annotation
animal
genomes.
The
zygote
has
a
daunting
task
ahead
of
itself;
it
must
develop
from
single
cell
(fertilized
egg)
into
fully
functioning
adult
with
multitude
different
types.
In
the
beginning,
help
its
mother,
in
form
gene
products
deposited
egg,
but
eventually,
rely
on
own
resources
to
proceed
through
development.
transfer
developmental
control
mother
embryo
is
called
maternal-to-zygotic
transition
(MZT).
All
animals
undergo
this
transition,
which
defined
by
two
main
processes-the
degradation
maternal
RNAs
and
synthesis
new
zygote's
genome.
Here,
we
review
regulation
MZT
Drosophila,
given
broad
conservation
essential
process,
much
shared
among
metazoans.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 7, 2024
Summary
A
central
problem
in
gene
regulation
is
to
discriminate
regulatory
functions
of
chromatin
composition
from
the
one
chromatin-modifying
complexes.
This
question
has
been
virtually
unexplored
context
H2A.Z
histone
variant
and
its
incorporation
into
nucleosomes
by
Snf2
Related
CREBBP
Activator
Protein
(SRCAP)
complex.
Here
we
combine
rapid
SRCAP
depletion,
a
mutant
lacking
deposition
activity,
quantitative
genome-wide
approaches
dissect
how
regulate
transcription
pluripotent
stem
cells.
We
find
that
exhibits
essential
H2A.Z-independent
preventing
DNA
binding
lineage-specific
factors
at
enhancers
stimulating
factor
promoters.
In
contrast,
acts
mainly
as
transcriptional
repressor
requires
dynamic
reloading
throughout
cell
cycle.
Our
study
demonstrates
SRCAP-H2A.Z
axis
broadly
orchestrates
promote
self-renewal,
inhibit
differentiation,
maintain
plasticity
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 5, 2024
Summary
Immediately
after
fertilization
the
genome
is
transcriptionally
quiescent.
Maternally
encoded
pioneer
transcription
factors
reprogram
chromatin
state
and
facilitate
of
zygotic
genome.
In
Drosophila
,
initiated
by
factor
Zelda.
While
Zelda-occupied
sites
are
enriched
with
histone
acetylation,
a
post-translational
mark
associated
active
cis
-regulatory
regions,
functional
relationship
between
Zelda
acetylation
in
activation
remained
unclear.
We
show
that
Zelda-mediated
recruitment
acetyltransferase
CBP
essential
for
transcription.
catalytic
activity
necessary
release
RNA
Polymerase
II
(Pol
II)
into
elongation
embryonic
development.
However,
also
activates
independent
through
Pol
recruitment.
Neither
nor
required
pioneering
function
Our
data
suggest
factor-mediated
conserved
mechanism
to
activate
but
this
role
separable
from
restructuring
accessibility.
Differential
gene
transcription
enables
development
and
homeostasis
in
all
animals
is
regulated
by
two
major
classes
of
distal
cis-regulatory
DNA
elements
(CREs):
enhancers
silencers.
Although
have
been
thoroughly
characterized,
the
properties
mechanisms
silencers
remain
largely
unknown.
By
an
unbiased
genome-wide
functional
screen
Drosophila
melanogaster
S2
cells,
we
discover
a
class
that
bind
one
three
factors
(TFs)
are
generally
not
included
chromatin-defined
CRE
catalogs
as
they
mostly
lack
detectable
accessibility.
The
silencer-binding
TF
CG11247,
which
term
Saft,
safeguards
cell
fate
decisions
vivo
functions
via
highly
conserved
domain
zinc-finger-associated
C-terminal
(ZAC)
corepressor
G9a,
independently
G9a's
H3K9-methyltransferase
activity.
Overall,
our
identification
with
unexpected
has
important
implications
for
understanding
future
study
repressive
CREs,
well
annotation
animal
genomes.