Download dr maternal dalam sitoplasma sel embrio akan memicu proses

CELL
DIFFERENTIATION
Differentiation
The development of specialized cell type from the
single fertilized egg.
Determination
The process wherein the fate of the cell becomes
committed.
overt change in cellular biochemistry and function
2 major ways of determination
1. CYTOPLASMIC SEGREGATION OF
DETERMINATIVE MOLECULES
The cleavage plane separate qualitatively
different region of the zygote cytoplasma into
daughter cells.
2. EMBRYONIC INDUCTION
involves the interaction of cells/tissues to
determine the fate of one or both of the
participants
Diferensiasi
Perubahan pola ekspresi protein sel selama
perkembangan dan pembelahan
Diferensiasi seringkali bersifat irreversible.
Diferensiasi terjadi pd tingkat molekuler krn
adanya ekspresi gen utk menghasilkan protein
tertentu
contoh: sel otot  aktin & miosin
sel β pankreas  insulin
Pengaturan inisiasi diferensiasi
1. Molekul (mRNA) dr maternal dalam sitoplasma
sel embrio akan memicu proses transkripsi
genom embrio
Sitoplasma sel telur mengandung mRNA,
protein & bahan-bahan lainnya yg berasal dr
maternal  berpengaruh thdp awal
perkembangan embrio
2. Signal yg dikode oleh genom dari sel embrio
lainnya akan menginduksi target sel
Lingkungan di sekitar sel :
informasi (signal) berupa molekul kimiawi yg
dikode oleh gen embrio
molekul dikirim ke sel target
perubahan pd sel target
(proses induksi)
DIFUSI MOLEKUL
SIGNAL
PROSES
INDUKSI
INTERAKSI
PERMUKAAN SEL
Struktur membran sel, mengandung :
1. molekul adesi sel
2. molekul adesi substrat
3. molekul junctional sel
4. molekul reseptor
Permukaan membran sel berubah
sejalan waktu dan tempat
Example of differentiation model
EKSPRESI GEN DAN PENGARUH
LINGKUNGAN
Diferensiasi dikontrol oleh program genetik &
dapat dimodifikasi oleh faktor lingkungan
Setiap sel memiliki komplemen penuh DNA
Sel-sel yg berbeda memiliki DNA yg sama.
Gen tertentu dalam beberapa sel harus ON dan
pada sel lain OFF.
Gen ON atau OFF
Faktor utama pengatur aktivasi gen
1. Bahan Inti / NUCLEUS
2. Bahan SITOPLASMA
NUCLEUS
Pengaturan Ekspresi Gen
Ada 2 mekanisme utama yg terlibat dalam
terjadinya imprinting, yakni:
1. Modifikasi Asetilasi Histone
2. Modifikasi Metilasi DNA
Asetilasi HISTONE
(Aktif transkripsi)
Modifikasi Metilasi DNA
Pd embrio preimplantasi terjadi perubahan mayor
melalui mekanisme imprinting yakni metilasi DNA
Perubahan metilasi DNA diwariskan secara stabil
melalui pembelahan sel shg akan tetap sampai
tahap fetus.
METILASI DNA
deaminasi
metilasi
Penambahan CH3 pada cytosine  Silencing Gene
Expression
Metilasi residu cytosine  5-methylcytosine
Deaminasi 5-methylcytosine  thymine.
Sel somatis pd mamalia memiliki 2 copy genome
(diploid)
Kontribusi nyata yg diberikan induk jantan &
betina pada anak-anaknya  berbeda-beda
Bagaimana gen yang diwariskan dr maternal &
paternal berbeda ekspresi ?
Terjadi switch off (silencing) pd salah satu copy
gen induk
Genomic Imprinting
Genomic Imprinting, suatu proses EPIGENETIK yg
dinamis, yg terlibat dalam pengaturan ekspresi
sebagian kecil gen dari genome mamalia melalui
proses modifikasi STRUKTUR DNA
Memberikan efek terhadap fenotip
Pd setiap generasi harus mampu di HAPUS (Off) dan
BENTUK (On)
Epigenetic reprogramming in germ cells is critical
for imprinting, and reprogramming in early
embryos also affects imprinting.
In germline cells the imprint is erased, and then reestablished according to the sex of the individual;
i.e. in the developing sperm, a paternal imprint is
established, whereas in developing oocytes, a
maternal imprint is established.
The process of erase and reprogramming is
necessary such that the current imprinting
status is relevant to the sex of the individual.
Asetilasi residu lisine pd posisi terminus dr protein histone
menghilangkan muatan positif  mengurangi afinitas
protein histon ke DNA
Enzim polimerase RNA polymerase dan faktor transkripsi
lebih mudah berikatan pada promoter
Umumnya, asetilasi histon memicu transkripsi;
deasetilasi histon menekan transkripsi
Acetylation (or ethanoylation): reaction that
introduces an acetyl functional group into an
organic compound.
Deacetylation is the removal of the acetyl group.
Introducing an acetyl group into a compound, the
substitution of an acetyl group for an active
hydrogen atom.
A reaction involving the replacement of the
hydrogen atom of a hydroxyl group with an acetyl
group (CH3 CO) yields a specific ester, the acetate.
Acetic anhydride is commonly used as an
acetylating agent reacting with free hydroxyl
groups.
Acetylation of proteins
In biology, i.e. in living cells, acetylation occurs as
a post-translational modification of proteins, for
example, histones and tubulins.
Histone Acetylation and Deacetylation
In histone acetylation and deacetylation, the
histones are acetylated and deacetylated on
lysine residues in the N-terminal tail as part of
gene regulation.
Typically, these reactions are catalyzed by
enzymes with "histone acetyltransferase" (HAt) or
"histone deacetylase" (HDAc OR HDs) activity.
Several different forms of HATs and HDs have been
identified.
Among them, CBP/p300 is probably the most
important, since it can interact with numerous
transcription regulators.
METILASI DNA
deaminasi
metilasi
Penambahan CH3 pada cytosine  Silencing Gene
Expression
Metilasi residu cytosine  5-methylcytosine
Deaminasi 5-methylcytosine  thymine.
Pola Metilasi DNA di-program kembali
(reprogramming) pada 2 periode perkembangan,
yakni:
- pada germ cells
- pad embrio preimplantation
Jika terjadi kerusakan/ gangguan dalam proses
atau pemeliharaan imprinting pd masa
perkembangan embrio preimplantasi (kultur atau
manipulasi embrio), dapat mengakibatkan:
- Fetal Loss atau
- Large Offspring Syndrome.
Methylation is a process that is used to control
gene expression, and it is what determines the
timing of gene expression
(as in embryologic development, in which genes
are turned on and off in a sequential fashion),
inactivation of an X-chromosome in a female
("Lyonization"), and, in mammals, differential
expression of certain genes depending upon
whether they are maternally- or paternally-derived
("genomic imprinting").
DNA METHYLATION
After replication, daughter strands of fully methylated DNA are
hemimethylated (reaction 3) and the original pattern of DNA methylation
is maintained by the DNA methyltransferase (reaction 2), which
preferentially methylates the cytosine residues at hemimethylated CpG
sites.
Further replication without methylation of the hemimethylated DNA
results in fully unmethylated DNA (reaction 4).
De novo methylation (reaction 1) is also considered to be mediated by
the DNA methyltransferase, although the efficiency of de novo
methylation is low.
(Goto and Monk, 1998)
Regulation
The grouping of imprinted genes within clusters allows
them to share common regulatory elements, such as noncoding RNAs and differentially methylated regions (DMRs).
When these regulatory elements control the imprinting of
several genes in a given region, they are known as
imprinting control regions (ICR).
The expression of non-coding RNAs, such as Air on
mouse chromosome 17 and KCNQ1OT1 on human
chromosome 11p15.5, have been shown to be essential for
the imprinting of genes in their corresponding regions.
V. FENOTIPE, FENOKOPI, PLEIOTROPISM
GEN: Fragmen DNA yg mengkode suatu polipeptida
LOKUS : Lokasi gen pada kromosom
Kepentingan Lokus: Terapi gen & Rekayasa gen
Perbedaan antara linked & Unlinked Gene:
Linked gen: terletak pada kromosom yg sama;
Unllinked gen: terletak pada kromosom yang
berbeda.
IDW
Hubungan antara GEN, ALLEL, & TRAITS (karakter)
GEN mempresentasikan traits
ALLELES = GENOTYPE  PHENOTYPE
T,t
Tinggi tanaman
T=tinggi / t=pendek
Interaksi ALEL akan menentukan karakter
Pada @ GEN, Individu diploid memiliki maks 2 Alel
Jk kedua alel sama  organisme disebut
HOMOZYGOUS
Jk kedua alel beda  HEROZYGOUS.
IDW
FENOKOPI  keadaan fenotipe yg dipengaruhi
oleh faktor eksternal
PLEIOTROPISM  gen tunggal yg memiliki multi
efek
IDW