Genome-Wide Characterization of Menin-Dependent H3K4me3 Reveals a Specific Role for Menin

Genome-Wide Characterization of Menin-Dependent H3K4me3 Reveals a Specific Role for Menin in the Regulation of Genes Implicated in MEN1-Like Tumors
-S Agarwal, R Jothi
PLoS ONE 7(5): e37952. doi:10.1371/journal.pone.0037952

The Genetics of Pituitary Adenomas

The Genetics of Pituitary Adenomas
-Monica Fedele, Giovanna Maria Pierantoni and Alfredo Fusco (2011). The Genetics of Pituitary Adenomas, Contemporary Aspects of Endocrinology, Dr. Evanthia Diamanti-Kandarakis (Ed.), ISBN: 978-953-307-357-6, InTech, Available from: http://www.intechopen.com/books/contemporary-aspects-of-endocrinology/the-genetics-of-pituitary-adenomas

DNA - A Graphic Guide to the Molecule that Shook the World

DNA - A Graphic Guide to the Molecule that Shook the World
-Rosenfield I, et al. 2011 Columbia University Press. ISBN 978-0-231-14270-0

• Don't let the 'comic book' design of this book fool You. This book is a great introduction to DNA and genetics! It's well written -even fun- and it has been extremely helpful in learning the basics of DNA structure, gene transcription, and more. Recommended.

Cells use DNA methylation to control gene expression

• "Methylation of DNA (not to be confused with histone methylation) is a common epigenetic signaling tool that cells use to lock genes in the 'off' position."
• DNA methylation occurs at the cytosine bases of eukaryotic DNA, which are converted to 5-methylcytosine by DNA methyltransferase (DNMT) enzymes.
• ...methylation near gene promoters varies considerably depending on cell type, with more methylation of promoters correlating with low or no transcription.
• Although patterns of DNA methylation appear to be relatively stable in somatic cells, patterns of histone methylation can change rapidly during the course of the cell cycle. Despite this difference, several studies have indicated that DNA methylation and histone methylation at certain positions are connected.
• Tumor suppressor genes are often silenced in cancer cells due to hypermethylation.

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The Role of Methylation in Gene Expression. Theresa Phillips, Ph.D. 2008, Nature Education.

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