Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
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