Abstract
Histones are constitutive components of nucleosomes and key regulators of chromatin structure. We previously observed that an extrachromosomal histone H2B (ecH2B) localizes at the intercellular bridge (ICB) connecting the two daughter cells during cytokinesis independently of DNA and RNA. Here, we show that ecH2B binds and colocalizes with CHMP4B, a key component of the ESCRT-III machinery responsible for abscission, the final step of cell division. Abscission requires the formation of an abscission site at the ICB where the ESCRT-III complex organizes into narrowing cortical helices that drive the physical separation of sibling cells. ecH2B depletion does not prevent membrane cleavage rather results in abscission delay and accumulation of abnormally long and thin ICBs. In the absence of ecH2B, CHMP4B and other components of the fission machinery, such as IST1 and Spastin, are recruited to the ICB and localize at the midbody. However, in the late stage of abscission, these fission factors fail to re-localize at the periphery of the midbody and the abscission site fails to form. These results show that extrachromosomal activity of histone H2B is required in the formation of the abscission site and the proper localization of the fission machinery.
Highlights
Histones are the constitutive components of nucleosomes, the basic units of DNA packaging in eukaryotes, and their post-translational modifications regulate chromatin structure and activity. [1,2].In mammals, there are different functional copies of the histone genes, which are located in a few clusters and encode several histone variants whose specific contribution to chromatin regulation is becoming clear [3,4,5,6,7]
These results show that extrachromosomal activity of histone H2B is required in the formation of the abscission site and the proper localization of the fission machinery
We previously identified an extrachromosomal localization of histone H2B at the intercellular bridge (ICB) during cytokinesis [13]
Summary
Histones are the constitutive components of nucleosomes, the basic units of DNA packaging in eukaryotes, and their post-translational modifications regulate chromatin structure and activity. There are different functional copies of the histone genes, which are located in a few clusters and encode several histone variants whose specific contribution to chromatin regulation is becoming clear [3,4,5,6,7]. In addition to chromatin structure and function, extrachromosomal activities of histones are emerging. In response to apoptotic stimuli, extrachromosomal histone H1.2 was shown to translocate into the cytoplasm and induce cytochrome C release from mitochondria [8] while histone. In antiviral innate immune response, ecH2B was shown to contribute to sense DNA-virus genomes and induce the cytoplasmic IFN-β response [10,11].
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