Histone octamers are represented by circles and the DNA is shown in black lines. HDAC is recruited to gene promoters by nonhistone proteins including methylated DNA-binding protein MeCP2, ER, methyl transferases (DNMT) and transcription factors (E2F, Rb). HDAC removes the acetyl group from nonhistone as well as histone proteins, which leads to chromatin conformational change and transcription repression of tumor-suppression genes. The loss of tumor-suppressor gene products contributes to the block of cell differentiation, uncontrolled cell proliferation, interrupted apoptosis and, ultimately, tumor formation.
ER: Estrogen receptor; HDAC: Histone deacetylase;
Rb: Retinoblastoma protein.