Histone H3 variants and modifications on transcribed genes

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Abstract
Chromatin structure is disrupted by the process of gene transcription, and the state of the histones plays an important role in gene regulation. Transcribing genes tend to be marked by specific histone modifications that are thought to modulate transcriptional activity. Recently, Ahmad and Henikoff (1) found that transcribed genes in Drosophila are also enriched for histone variant H3.3, which is deposited in chromatin through a DNA replication-independent nucleosome assembly pathway. In an article from the same group in this issue of PNAS, McKittrick et al. (2) demonstrate that a Drosophila cell line contains enough H3.3 to package all of the transcribed genes and that H3.3 is enriched in modifications associated with transcription (e.g., acetylation of select lysines and methylation of lysine 4). Lysine 9 methylation, which is abundant in transcriptionally silent heterochromatin, occurs primarily on the major form of H3 that is assembled into nucleosomes by the replication-dependent pathway. These results led McKittrick et al. to propose that the modification state of H3 associated with a gene is tied to the pathway that assembled the gene into nucleosomes. This hypothesis could also account for observations made by Waterborg (3) 13 years ago, who found that acetylated lysines and lysine 4 methylation are enriched in the alfalfa variant H3.2, whereas lysine 9 methylation was found primarily in the major form, H3.1. McKittrick et al. extracted histones from Drosophila Kc cells and separated H3.3 from H3 on a reverse-phase HPLC column. These proteins differ in only 4 aa, and antibodies that can distinguish between them are not available. …