RAMB - Fevereiro 2017

omes

KMS

186

ssoc

ras

2017; 63(2):180-189

FIGURE 1

Epigenetic factors and iPSC reprogramming efficiency. The ectopic expression of Yamanaka factors, Oct4, Sox2, Klf4 and c-Myc (OSKM) are able to lead to DNA demethylation and

reprogramming of somatic cells. A. The use of Tet1 (DNA hydroxylase) and of 5-azacytidine (inhibitor of the enzyme DNA methyltransferase) improves the reprogramming efficiency of iPSC cells. B.

The use of valproic acid (VPA), BIX-01294 and vitamin C favors reprogramming through inhibition of histone deacetylase (HDAC), histone methyltransferase (G9a) and activation of the deme-

thylases Kdm3/Kdm4, respectively. C. miRNAs 302-367, 290-295, 135b are able to increase reprogramming efficiency by promoting the progression of the cell cycle. miR Let-7 inhibits the cell cycle,

and miR-34 inhibits the translation of p53, decreasing reprogramming efficiency.

Acetyl

Sox2 Klf4

C-myc

Oct4

Tet1

miRNA

DNA

Histone

Chromosome

Methyl

Hydroxyl

Unmethylated

5-azacytidine

miR Let-7

miR-34

miR 302

∼

367

miR 290

∼

295

miR 135b

Kdm3/

Kdm4

HDAC

VPA

BIX-01294

Vitamin C

5-methylcytosine (5mC)

Unmethylated cytosine

DNMT1

Histone

deacetylase

Histone

methyltransferase

DNA

methyltransferase

inhibitor

miRNA

Chemical compound/

Molecule

–

G9a