Epigenetic control of skull morphogenesis by histone deacetylase 8

The field of epigenetics is primarily concerned with the ability for genes to be turned “off” or “on” – in other words, the study of how genes can be made accessible or inaccessible by the body and how that affects development, functioning and regulation of important biological processes. One of the major groups proteins which prevents ‘access’ of a gene, are called Histone deacetylases, whose primary effects are to tighten chromatin, preventing genes on that chromatin from being expressed in cells.

This paper, entitled Epigenetic control of skull morphogenesis by histone deacetylase 8, by Haberland, Mokalled, Montgomery and Olson, 2009, examines the role of a Histone deacetylase 8 (Hdac8) in skull formation in mice. The team created a mouse with a Hdac8 deletion, resulting in severe deficiency of Neural Crest Cells (NCCs) resulting in a loss of cranial bone structure – thus the Hdac8 mutation is lethal. The Hdac8 mutant NCC cells were examined and it was found that pathways related to neurogenesis and the production of cytoskeletal proteins were upregulated.

The paper identifies two genes, Otx2 and Lhxl, which are affected by the lack of Hdac8, which could be at the root of the frontal skull dysmorphism.
The paper also examines implications for human health – Hdac inhibitors, a relatively recent class of medicines, have been implicated as a possible cause of increased occurrences of facial abnormalities in infants born from mothers taking such inhibitors.

By

MARK PHILLIPPS

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