Bookmarking promoters in mitotic chromatin: poly(ADP-ribose)polymerase-1 as an epigenetic mark.
Bottom Line: After mitosis, it is thought that bookmarking transcription factors remain at promoters, regulating which genes become active and which remain silent.Herein, we demonstrate that poly(ADP-ribose)polymerase-1 (PARP-1) is a genome-wide epigenetic memory mark in mitotic chromatin, and we further show that the presence of PARP-1 is absolutely crucial for reactivation of transcription after mitosis.Based on these findings, a novel molecular model of epigenetic memory transmission through the cell cycle is proposed.
Affiliation: Fox Chase Cancer Center, Philadelphia, PA, 19111 USA.Show MeSH
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Mentions: We first compared the PARP-1 protein distribution in interphase chromatin and metaphase-arrested chromosomes (Figure 1A), confirming the metaphase status of DNA by co-staining with phosphoH3/Ser10, a well-known marker of mitotic chromatin (43) (Supplementary Figure S1). PARP-1 remained bound to condensed chromatin during mitosis (Figure 1A). To assess the distribution PARP-1 in metaphase chromatin, we performed ultrastructural analysis of metaphase chromosomes using immuno-electron microscopy (EM) (37) and immunofluorescence. EM immunocytochemistry deploying anti-PARP-1 and the antibody to linker histone H1 (Figures 1B–D) revealed a number of well-defined domains in the condensed chromatin occupied by PARP-1. Confocal microscopy (Figure 1E) confirmed that PARP-1 and H1 localized to distinct non-overlapping blocks in mitotic chromatin (Figure 1E). Similar anti-correlation in PARP-1 and H1 distributions has been previously observed in interphase chromatin (28,35).
Affiliation: Fox Chase Cancer Center, Philadelphia, PA, 19111 USA.