A chromatin writer's block

Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. This material includes histones, the core proteins around which are tightly wound DNA. I used to think all the information that genetically defines organisms is contained in DNA. Apparently this is not the case. The core histones also are capable of storing epigenetic information. They can written upon, read, and erased by other molecules. These messages affect the expression and silencing of genes without altering the underlying nucleotide sequence.

• MLL (mixed-lineage leukemia) is a writer of H3K4me3, the histone H3K4 trimethylation mark.
• Menin is important for the writing of H3K4me3.
• Menin contains a LLWLL amino acid motif, which "is in fact a nuclear receptor interaction domain."
• Reduction of menin mRNA levels... results in reduced levels of H3K4 trimethylation on hormone responsive genes and decreased transcription of these genes.
• In MEN1 tumors, writing of H3K4me3 on specific target genes is blocked.
• Loss of H3K4 trimethylation appears to contribute to MEN1 tumor development.
• As loss of menin function leads to reduced H3K4me3 levels on target genes an inhibitor of H3K4 demethylase activity, causing persistence of remaining H3K4 trimethylation, could be an effective approach. Compounds that interfere with the removal of the histone methylation mark are being developed.
• Histone deacetylase inhibitors (HDACis) are a well-known class of histone modification regulating drugs, with very promising effects in preclinical and clinical studies.
• Specific targeting of menin-HMT to treat tumors poses a great challenge for future research.

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Multiple endocrine neoplasia type 1: a chromatin writer’s block. Dreijerink, K. M. A., Lips, C. J. M. and Timmers, H. T. M. (2009). Journal of Internal Medicine, 266: 53–59. doi: 10.1111/j.1365-2796.2009.02115.x
Mixed-lineage lukemia. Wikipedia