REGULASI EKSPRESI GEN

Andriani Dept. Biokimia dan Biologi Molekuler

FK UNTAN

EKSPRESI GEN

- Dari keseluruhan genom, ekspresi sebuah gen berlangsung pada suatu waktu saat diperlukan

- Keseimbangan jumlah protein dalam sel diatur oleh mekanisme :1. Transkripsi 2. Posttranscriptional modification of mRNA3. Messenger RNA degradation4. Protein synthesis (translation)5. Posttranslational modification of proteins6. Protein targeting and transport7. Protein degradation

EKSPRESI GEN

• Housekeeping gene : jumlah konstan dalam sel • Regulated gene expression : jumlah bisa

meningkat dan menurun tergantung sinyal INDUKSI (Positive Regulation)→ proses

peningkatan ekspresiREPRESI (Negative Regulation) → penurunan

ekspresi Dobel negative ~ INDUKSI

DOGMA SENTRAL

DNA

RNA

Protein

REGULASI GEN PADA PROKARIOTA

• Model mempelajari regulasi ekspresi pada E. Coli

• Bakteri mensintesis enzim berdasarkan nutrisi pada lingkungannya

• Selain glukosa dan laktosa, juga memerlukan aa triptofan

• Ketika E. Coli berada pada medium triptofan, akan diabsorbsi

• Jika triptofan (-) , sintesis

• OPERON : - Situs promotor : tempat melekatnya RNA

polymerase dan awal transkripsi - Daerah terbentuknya repressor • Operator berada pada DNA diantara promotor dan

gen struktural yang akan di transkripsi

OPERON TRIPTOFAN

• Aa triptofan dikode 5 gen struktural • RNA polimerase terikat pada promotor (pada

permulaan gen pertama) • Mekanisme on-off

OPERON LAC

• Selain aa, E. Coli mencerna gula laktosa pada lingkungan (jacques Monod dan Francois Jacob)

• E. Coli mengekspresikan beta galaktosidase untuk mencerna laktosa

Lac Z gene

• Pengaturan ekspresi Beta galaktosidase dilakukan oleh protein regulator : repressor

• Represor terikat pada gen Lac Z pada daerah antara promotor dan start kodon gen struktural : operator

•

• Dalam keadaan normal (tanpa laktosa) repressor menduduki operator : OFF

• Dalam keadaan laktosa (+), repressor mengikat laktosa, : ON

REGULASI EKSPRESI GEN PADA EUKARIOTA

prokaryotes Eukaryotes

Respond Regulate

Short term Long term

Immediate environtment (external) Homeostasis(internal)

Survival of individual cell Needs of whole organism

Regulation in eukaryote can be regulated

at four distinct levels.

INTRONS AND EXONS• Eukaryotic DNA differs from prokaryotic

DNA it that the coding sequences along the gene are interspersed with noncoding sequences

• The coding sequences are called – EXONS

• The non coding sequences are called– INTRONS

INTRONS AND EXONS• After the initial transcript is produced

the introns are spliced out to form the completed message ready for translation

• Introns can be very large and numerous, so some genes are much bigger than the final processed mRNA

INTRONS AND EXONS• Muscular dystrophy

• DMD gene is about 2.5 million base pairs long

• Has more than 70 introns• The final mRNA is only about 17,000

base pairs long

RNA Splicing

• Provides a point where the expression of a gene can be controlled

• Exons can be spliced together in different ways• This allows a variety of different polypeptides to

be assembled from the same gene• Alternate splicing is common in insects and

vertebrates, where 2 or 3 different proteins are produced from one gene

MODIFIKASI KROMATIN

- Modifikasi melalui aa yang terdapat pada protein histon- Metilasi DNA : pada GC Rich sequence

ASETILASI PROTEIN HISTON

structural geneGCGC CAAT TATA

intronexon exon

start

CAAT box

GCbox

enhancer

cis-acting element

TATA box (Hogness box)

Cis-acting element

DNA BENDING PROTEIN

• Zinc fingers• B- zip protein• Helix turn helix • Helix loop helix

MODIFIKASI POST TRANSKRIPSI

TERIMA KASIH