Parathymosin affects the binding of linker histone H1 to nucleosomes and remodels chromatin structure.
Linker histone H1 is the major factor that stabilizes higher order chromatin structure and modulates the action of chromatin-remodeling enzymes. We have previously shown that parathymosin, an acidic, nuclear protein binds to histone H1 in vitro and in vivo. Confocal laser scanning microscopy reveals a nuclear punctuate staining of the endogenous protein in interphase cells, which is excluded from dense heterochromatic regions. Using an in vitro chromatin reconstitution system under physiological conditions, we show here that parathymosin (ParaT) inhibits the binding of H1 to chromatin in a dose-dependent manner. Consistent with these findings, H1-containing chromatin assembled in the presence of ParaT has reduced nucleosome spacing. These observations suggest that interaction of the two proteins might result in a conformational change of H1. Fluorescence spectroscopy and circular dichroism-based measurements on mixtures of H1 and ParaT confirm this hypothesis. Human sperm nuclei challenged with ParaT become highly decondensed, whereas overexpression of green fluorescent protein- or FLAG-tagged protein in HeLa cells induces global chromatin decondensation and increases the accessibility of chromatin to micrococcal nuclease digestion. Our data suggest a role of parathymosin in the remodeling of higher order chromatin structure through modulation of H1 interaction with nucleosomes and point to its involvement in chromatin-dependent functions.
Martic
Goran
G
Laboratory of Biological Chemistry, Medical School, University of Ioannina, 45110 Ioannina, Greece.
Karetsou
Zoe
Z
Kefala
Katerina
K
Politou
Anastasia S
AS
Clapier
Cedric R
CR
Straub
Tobias
T
Papamarcaki
Thomais
T
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D002942:Circular Dichroism; D006041:Goats; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013947:Thymosin / Q000031:analogs & derivatives* / Q000378:metabolism*
D006657:Histones; D009707:Nucleosomes; D013947:Thymosin; C044498:parathymosin alpha