H3K79me3T80ph is a Novel Histone Dual Modification and a Mitotic Indicator in Melanoma

Danielle R Martinez,Carlos A Torres-Cabala,Victor G Prieto,Hunter W Richards,Jonathan L Curry,Qiushi Lin,Estela E Medrano

doi:10.1155/2012/823534

Abstract

The current study characterizes the mitosis-associated histone dual modification on the core of histone H3: trimethylation of histone H3 lysine 79 and simultaneous phosphorylation of H3 threonine 80 (H3K79me3T80ph). Through the use of protein and microscopy-based techniques, we find that H3K79me3T80ph shares a similar spatial and temporal regulation as H3S10ph but additionally requires methyltransferase activity. In addition, we find that Aurora kinase activity is necessary for the catalysis of H3K79me3T80ph in vivo. Finally, our analysis of H3K79me3T80ph using a tissue microarray indicates that H3K79me3T80ph marks a subset of primary cutaneous melanomas with metastatic potential indicating that H3K79me3T80ph may identify a subset of invasive melanomas with a more aggressive clinical behaviour.

Highlights

The nucleosome is the fundamental unit of chromatin; it consists of an octamer of core histones proteins (2 molecules each of H3, H4, H2A, and H2B) around which DNA is wrapped
Through the use of cell synchronization experiments, flow cytometry, and immunofluorescence studies, we have found that H3K79me3T80ph is a novel histone dual modification in the core of histone H3
This is further supported by our immunofluorescence studies showing that H3K79me3T80p shares the same temporal regulation as H3S10ph, which is known to appear in late G2 [7]

Summary

Introduction

The nucleosome is the fundamental unit of chromatin; it consists of an octamer of core histones proteins (2 molecules each of H3, H4, H2A, and H2B) around which DNA is wrapped. Lysine residues on histone H3 can be mono-, di-, or trimethylated (me, me2, and me resp.), with the majority of H3 methylation marks residing on the N-terminal tail of H3 [1]. On the tail of H3, three methylatable lysines lie adjacent to residues that have been found to be phosphorylated during mitosis, T3/K4, K9/S10, and K27/S28 [6,7,8]. It is not clear in what capacity lysine methylation and the adjacent phosphorylations occur together during mitosis or what the role is of these methyl-phospho modifications

Methods

Results

Conclusion