Recent studies have focused their attention on the structure and function of histone chaperones involved in different aspects of somatic chromatin assembly and disassembly. However, one of the most dramatic chromatin remodeling processes takes place immediately after fertilization and is mediated by proteins in metazoan eggs that function as histone chaperones and histone storage proteins. These include members of the nucleoplasmin (NPM) family and the nuclear autoantigenic sperm protein (NASP) families. While it had been know for some time that these proteins function as “histone sinks”, new studies are shedding light on their role as histone chaperones.
NASP was first identified in Xenopus laevis eggs where it accumulated in the nucleoplasm and was found to bind histones H3 and H4 at which time it believed to act simply as a histone storage protein. Interestingly, in addition to binding and providing storage to H3-H4 in the egg and in somatic cells, our studies have shown NASP to be the first characterized chaperone for histone H1. The members of the histone H1 family (linker histones) are essential to maintaining the structure of chromatin with respect to the folding of the chromatin fiber, nucleosome spacing, chromatin remodeling, gene transcription and progression through the cell cycle. Until recently there has been no histone H1 chaperone characterized and no evidence of a storage protein to which linker histones are bound, when not associated with DNA of NCPs. By using recombinant NASP, to incorporate linker histones onto the nucleosome arrays in a chromatin fiber, we studied the dynamics and conformation of chromatin in a more biologically relevant and precise method than presented in any previous chromatin research.
Like NASP, nucleoplasmin was identified as a factor in X. laevis eggs that binds histones and loads them onto DNA. Subsequently, the nucleoplasmin protein family has been to be universally represented throughout metazoans where it plays a similar role in chromatin metabolism. Members of this family include nucleophosmin (NPM1), nucleoplasmin (NPM2, NPM or Np), the newly characterized NPM3 and nucleoplasmin-like proteins (NPM-like or NLP). We have been able to demonstrate that NPM2 that is highly phosphorylated in X. laevis eggs can unfold sperm and somatic chromatin by facilitating the removal of linker histones and other chromosomal proteins from linker DNA regions between nucleosomes in the absence of any stable interaction with the nucleosome core particle (NCP) itself. In addition, our studies reveal that NPM2 is a pentameric chaperone, as opposed to a decameric chaperone, that regulates the condensation state of sperm and somatic chromatin by removing linker histones and specific nuclear basic proteins and depositing histone H2A-H2B dimers on the distal face of the NPM2. / Graduate
| Identifer | oai:union.ndltd.org:uvic.ca/oai:dspace.library.uvic.ca:1828/4387 |
| Date | 20 December 2012 |
| Creators | Finn, Ron |
| Contributors | Ausio, Juan |
| Source Sets | University of Victoria |
| Language | English, English |
| Detected Language | English |
| Type | Thesis |
| Rights | Available to the World Wide Web |
Page generated in 0.0027 seconds