Genes & Development,
Год журнала:
2016,
Номер
30(16), С. 1866 - 1880
Опубликована: Авг. 15, 2016
A
defining
feature
of
heterochromatin
is
methylation
Lys9
histone
H3
(H3K9me),
a
binding
site
for
protein
1
(HP1).
Although
H3K9
methyltransferases
and
HP1
are
necessary
proper
structure,
the
specific
contribution
to
function
animal
development
unknown.
Using
our
recently
developed
platform
engineer
genes
in
Drosophila,
we
generated
H3K9R
mutant
flies,
separating
functions
nonhistone
substrates
methyltransferases.
Nucleosome
occupancy
HP1a
at
pericentromeric
markedly
decreased
mutants.
Despite
these
changes
chromosome
architecture,
small
percentage
mutants
complete
development.
Consistent
with
this
result,
expression
most
protein-coding
genes,
including
those
within
heterochromatin,
similar
between
controls.
In
contrast,
exhibit
increased
open
chromatin
transcription
from
piRNA
clusters
transposons,
resulting
transposon
mobilization.
Hence,
silencing
major
developmental
H3K9.
RNA Biology,
Год журнала:
2017,
Номер
14(6), С. 726 - 738
Опубликована: Янв. 6, 2017
Metazoan
replication-dependent
(RD)
histone
genes
encode
the
only
known
cellular
mRNAs
that
are
not
polyadenylated.
These
end
instead
in
a
conserved
stem-loop,
which
is
formed
by
an
endonucleolytic
cleavage
of
pre-mRNA.
The
for
all
5
proteins
clustered
metazoans
and
coordinately
regulated
with
high
levels
expression
during
S
phase.
Production
occurs
nuclear
body
called
Histone
Locus
Body
(HLB),
subdomain
nucleus
defined
concentration
factors
necessary
gene
transcription
pre-mRNA
processing.
include
scaffolding
protein
NPAT,
essential
transcription,
FLASH
U7
snRNP,
both
activated
Cyclin
E/Cdk2-mediated
phosphorylation
NPAT
at
G1-S
transition.
within
HLB
couples
processing,
enhancing
efficiency
mRNA
biosynthesis.
Repression
of
genes
by
Polycomb
requires
that
PRC2
modifies
their
chromatin
trimethylating
lysine
27
on
histone
H3
(H3K27me3).
At
transcriptionally
active
genes,
di-
and
tri-methylated
H3K36
inhibit
PRC2.
Here,
the
cryo-EM
structure
dinucleosomes
reveals
how
binding
its
catalytic
subunit
EZH2
to
nucleosomal
DNA
orients
N-terminus
via
an
extended
network
interactions
place
H3K27
into
site.
Unmodified
occupies
a
critical
position
in
EZH2-DNA
interface.
Mutation
arginine
or
alanine
inhibits
methylation
nucleosomes
vitro
.
Accordingly,
Drosophila
H3K36A
H3K36R
mutants
show
reduced
levels
H3K27me3
defective
repression
HOX
genes.
The
relay
between
EZH2,
therefore
creates
geometry
permits
allosteric
inhibition
methylated
chromatin.
Genes & Development,
Год журнала:
2016,
Номер
30(9), С. 1116 - 1127
Опубликована: Май 1, 2016
Polycomb
group
(PcG)
protein
complexes
repress
transcription
by
modifying
target
gene
chromatin.
In
Drosophila,
this
repression
requires
association
of
PcG
with
cis-regulatory
response
elements
(PREs),
but
the
interactions
permitting
formation
these
assemblies
are
poorly
understood.
We
show
that
Sfmbt
subunit
DNA-binding
Pho-repressive
complex
(PhoRC)
and
Scm
canonical
Polycomb-repressive
1
(PRC1)
directly
bind
each
other
through
their
SAM
domains.
The
1.9
Å
crystal
structure
Scm-SAM:Sfmbt-SAM
reveals
recognition
mechanism
shows
Sfmbt-SAM
lacks
polymerization
capacity
domains
its
PRC1
partner
subunit,
Ph.
Functional
analyses
in
Drosophila
demonstrate
Scm-SAM
essential
for
PhoRC
DNA
binding
is
critical
to
initiate
PREs.
Together,
suggests
PRE-tethered
nucleates
recruitment
Scm-SAM/Ph-SAM-mediated
then
results
PRC1-compacted
