Changes in global histone modifications during dedifferentiation in newt lens regeneration

PURPOSE: Reprogramming of pigmented epithelial cells (PECs) is a decisive process in newt lens regeneration. After lens removal PECs in dorsal iris dedifferentiate and revert to stem cell-like cells, and transdifferentiate into lens cells. Our purpose is to know how global histone modifications are regulated in the reprogramming of PECs. METHODS: Iris sections were stained using various histone modification-specific antibodies. The intensity of stained signal in nucleus of PECs was measured and changes in histone modification during dedifferentiation were evaluated. RESULTS: During dedifferentiation of PECs histone modifications related to gene activation were differentially regulated. Although tri-methylated histone H3 lysine 4 (TriMeH3K4) and acetylated histone H4 (AcH4) were increased, acetylated histone H3 lysine 9 (AcH3K9) was decreased during dedifferentiation. Among all gene repression-related modifications analyzed only tri-methylated histone H3 lysine 27 (TriMeH3K27) showed a significant change. Although in the dorsal iris TriMeH3K27 was kept at same levels after lentectomy, in ventral iris it was increased. CONCLUSIONS: Histone modifications are dynamically changed during dedifferentiation of PECs. A coordination of gene activation-related modifications, increasing of TriMeH3K4 and AcH4 and decreasing of AcH3K9, as well as regulation of TriMeH3K27, could be a hallmark of chromatin regulation during newt dedifferentiation.