Adult stem cells modulate balance between proliferation, differentiation and cell death to maintain tissue homeostasis. We use Drosophila testes to study how germ cells transit from proliferation to differentiation, and repair DNA damage to prevent cell death. In testes, Cyclin B (CycB) accumulates in proliferating germ cells, decreases upon completion of mitosis, and regain expression just before meiotic G2/M transition. Transcriptional activation and translational repression of CycB in meiosis are well studied. But how CycB is downregulated after mitosis and if such downregulation is crucial remain unknown. Here we found chromatin factor E(Pc) transcriptionally represses CycB by modulating H4 acetylation and reduced CycB is essential for germ cell differentiation. Moreover, E(Pc) depletion causes accumulated DNA double strand breaks and severe germ cell death. In addition, lacking activity of Tip60 histone acetyltransferase (HAT) leads to similar defects. Taken together, acetylation plays crucial roles in maintaining tissue homeostasis though transcriptional regulation and DNA damage repair.