THESIS
2019
xi, 54 pages : illustrations (chiefly color) ; 30 cm
Abstract
Setdb1,
a
histone
3
lysine
9
(H3K9)
methyltransferase,
is
a
critical
epigenetic
regulator
during
various
developmental
progresses.
While
distinct
functions
have
been
described
in
diverse
tissues
and
species,
the
molecular
mechanism
by
which
it
can
carry
out
such
wide
range
of
tasks
is
poorly
understood.
Here,
I
aim
to
elucidate
the
roles
of
Setdb1
in
regulating
genome
organization
in
mouse
stem/progenitor
cells,
proviral
silencing
in
human
melanoma
and
transcription
control
in
Drosophila
germline
development.
Employing
epigenomic
tools
such
as
ChIP-‐seq,
RNA-‐seq,
Hi-‐C
and
bisulfite
sequencing,
in
addition
to
mining
publically
available
data,
I
discovered
several
novel
features
of
this...[
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Setdb1,
a
histone
3
lysine
9
(H3K9)
methyltransferase,
is
a
critical
epigenetic
regulator
during
various
developmental
progresses.
While
distinct
functions
have
been
described
in
diverse
tissues
and
species,
the
molecular
mechanism
by
which
it
can
carry
out
such
wide
range
of
tasks
is
poorly
understood.
Here,
I
aim
to
elucidate
the
roles
of
Setdb1
in
regulating
genome
organization
in
mouse
stem/progenitor
cells,
proviral
silencing
in
human
melanoma
and
transcription
control
in
Drosophila
germline
development.
Employing
epigenomic
tools
such
as
ChIP-‐seq,
RNA-‐seq,
Hi-‐C
and
bisulfite
sequencing,
in
addition
to
mining
publically
available
data,
I
discovered
several
novel
features
of
this
chromatin
modifier.
In
mESCs,
the
antagonistic
relationship
between
Setdb1
and
CTCF
suggests
the
role
of
Setdb1
in
maintenance
of
3D
genome
architecture
by
regulating
chromatin
loop
formations.
Furthermore,
in
human
melanoma
cells,
SETDB1
potentially
compensates
for
DNA
hypothethylation
in
repressing
repetitive
elements.
Finally,
in
Drosophila
melanogaster
ovaries,
dSETDB1
participates
in
germline
specific
transcriptional
silencing,
analogous
to
its
mammalian
counterpart.
Taken
together,
this
study
highlights
the
distinct
molecular
mechanisms
of
Setdb1
to
carry
out
its
diverse
roles
in
various
cell
types
by
interplaying
with
other
chromatin
modifiers.
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