Epigenetics: Could cancer sometimes be an outcome of failure?
|February 19, 2014||Posted by News under Epigenetics, News|
According to new research, epigenetic regulation is required to ensure correct number of chromosomes in the daughter cells after division.
Normally when a cell divides, the chromosomes are segregated equally to two daughter cells. However, tumor cells frequently have either too few or too many chromosomes, leading to the incorrect expression of a number of genes. When a cell is about to divide, the cell division machinery takes hold of chromosomes by the centromere so that they may be pulled apart and one copy of each given to the daughter cells.
In the current study, researchers have shown that an epigenetic process, involving the attachment of a small protein to the histone H2B (called H2Bub1), facilitates an important structural change of the centromere immediately prior to cell division. It was previously shown that enzymes that modify histone H2B in this way also play a role in protecting against cancer. This was previously linked to defects in chromosomal repair.
Abstract Functional centromeres are essential for proper cell division. Centromeres are established largely by epigenetic processes resulting in incorporation of the histone H3 variant CENP-A. Here, we demonstrate the direct involvement of H2B monoubiquitination, mediated by RNF20 in humans or Brl1 in Schizosaccharomyces pombe, in centromeric chromatin maintenance. Monoubiquinated H2B (H2Bub1) is needed for this maintenance, promoting noncoding transcription, centromere integrity and accurate chromosomal segregation. A transient pulse of centromeric H2Bub1 leads to RNA polymerase II–mediated transcription of the centromere’s central domain, coupled to decreased H3 stability. H2Bub1-deficient cells have centromere cores that, despite their intact centromeric heterochromatin barriers, exhibit characteristics of heterochromatin, such as silencing histone modifications, reduced nucleosome turnover and reduced levels of transcription. In the H2Bub1-deficient cells, centromere functionality is hampered, thus resulting in unequal chromosome segregation. Therefore, centromeric H2Bub1 is essential for maintaining active centromeric chromatin. – Laia Sadeghi, Lee Siggens, J Peter Svensson, Karl Ekwall. Centromeric histone H2B monoubiquitination promotes noncoding transcription and chromatin integrity. Nature Structural & Molecular Biology, 2014; DOI: 10.1038/nsmb.2776
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