Egr2-guided histone H2B monoubiquitination is required for peripheral nervous system myelination
Abstract
Schwann cells are the nerve ensheathing cells of the peripheral nervous system. Absence, loss and malfunction of Schwann cells or their myelin sheaths lead to peripheral neuropathies such as Charcot-Marie-Tooth disease in humans. During Schwann cell development and myelination chromatin is dramatically modified. However, impact and functional relevance of these modifications are poorly understood. Here, we analyzed histone H2B monoubiquitination as one such chromatin modification by conditionally deleting the Rnf40 subunit of the responsible E3 ligase in mice. Rnf40-deficient Schwann cells were arrested immediately before myelination or generated abnormally thin, unstable myelin, resulting in a peripheral neuropathy characterized by hypomyelination and progressive axonal degeneration. By combining sequencing techniques with functional studies we show that H2B monoubiquitination does not influence global gene expression patterns, but instead ensures selective high expression of myelin and lipid biosynthesis genes and proper repression of immaturity genes. This requires the specific recruitment of the Rnf40-containing E3 ligase by Egr2, the central transcriptional regulator of peripheral myelination, to its target genes. Our stud...Continue Reading
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Monoubiquitination of human histone H2B: the factors involved and their roles in HOX gene regulation
HDAC1 and HDAC2 control the transcriptional program of myelination and the survival of Schwann cells
Stem cell factor Sox2 and its close relative Sox3 have differentiation functions in oligodendrocytes
Loss of RNF40 Decreases NF-κB Activity in Colorectal Cancer Cells and Reduces Colitis Burden in Mice
Histone H2B monoubiquitination regulates heart development via epigenetic control of cilia motility.
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