Understanding the Reasons for Histone H3 K4 Trimethylation (H3K4Me3)

Mon, 06/18/2012 - 10:17

Epigenetic mechanisms allow distinction between the active and inactive compartments of the genome, allowing proper cell lineage and embryogenesis. The trimethylation of Histone 3 at lysine 4 (H3K4Me3) is a common epigenetic histone modification that occurs in close proximity to nearly two-thirds of human gene promoters, and seems to balance another modification, trimethylation at lysine 27 (H3K27Me3). Researchers have created global histone methylation maps for human ES cells by using an H3K4Me3 antibody for ChIP (chromatin immunoprecipitation) coupled with paired-end ditags sequencing and found that these two modifications work in tandem to differentiate and maintain stem cells (1).

Chromatin Immunoprecipitation: Histone H3

Similar ChIP studies in Xenopus embryos with a H3K4Me3 antibody to create a transcriptome genome-wide map of gastrulation showed striking spatially-regulated expression instead of the expected bivalency previously shown with expression profiles, sequential ChIP, and ChIP on dissected embryos (2).  This hierarchy within zygotic gene activation is also found in genome-wide promoter occupancy studies using an H3K4Me3 antibody  in mouse embryos (3) and in a survey of pluripotent, multipotent, and unipotent cell types(4). An intriguing finding linking H3K4Me3 to cancer, DNA damage repair, and apoptosis used an H3K4Me3 antibody to identify an association between H3K4Me3 and the tumor supressor Inhibitor of Growth 1 (ING1) (5). Disruption of this interaction through naturally occurring mutations found in human malignancies impaired ING1’s ability to induce nucleotide repair and cell death.

  1. PMID: 18371363
  2. PMID: 19758566
  3. PMID: 20161773
  4. PMID: 18477461
  5. PMID: 18533182

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