Nucleolin is a histone chaperone with FACT-like activity and assists remodeling of nucleosomes

Abstract

Remodeling machines play an essential role in the control of gene expression, but how their activity is regulated is not known. Here we report that the nuclear protein nucleolin possesses a histone chaperone activity and that this factor greatly enhances the activity of the chromatin remodeling machineries SWI/SNF and ACF. Interestingly, nucleolin is able to induce the remodeling by SWI/SNF of macroH2A, but not of H2ABbd nucleosomes, which are otherwise resistant to remodeling. This new histone chaperone promotes the destabilization of the histone octamer, helping the dissociation of a H2A-H2B dimer, and stimulates the SWI/SNF-mediated transfer of H2A-H2B dimers. Furthermore, nucleolin facilitates transcription through the nucleosome, which is reminiscent of the activity of the FACT complex. This work defines new functions for histone chaperones in chromatin remodeling and regulation of transcription and explains how nucleolin could act on transcription.

Characterization of AtNUC-L1 Reveals a Central Role of Nucleolin in Nucleolus Organization and Silencing of AtNUC-L2 Gene in Arabidopsis

“…Moreover, our results also show that AtNUC-L1 binds the rDNA promoter in vivo; consequently, we expect that the absence of AtNUC-L1 in mutant plants might also affect rDNA condensation and gene transcription. These observations are supported by a recent study demonstrating that Xenopus laevis nucleolin modifies chromatin structure and facilitates RNA Pol II transcription (Angelov et al, 2006).…”

“…Only two reports have described the effect of reduction of nucleolin in higher organisms. These reports revealed that reduction of the nucleolin by RNA interference (RNAi) in human cells increases expression of p53 protein (Takagi et al, 2005) and inhibits RNA polymerase I transcription (Angelov et al, 2006).…”

Histone chaperones in nucleosome eviction and histone exchange

“…However, it appears likely that many histone deposition factors will promote to some extent the reverse reaction of partial or complete nucleosome disassembly. This has been directly shown for NAP1, both in vitro and in vivo [30] [31] [32] [33], FACT (in vitro and in vivo; reviewed in [34]); Asf1 (in vivo; [35]), and nucleolin (in vitro; [36]). …”

“…For example, RSC disassembles a nucleosome in the presence of the histone chaperone NAP1, but not ASF1, suggesting the functional specificity of the individual histone chaperones [59]. SWI/SNF-dependent nucleosome remodeling is enhanced by nucleolin [36], and CHD1 cooperates with NAP1 in nucleosome disassembly at promoters and in coding regions [32]. SWR1, a complex that exchanges histone H2A.Z into assembled chromatin co-opts either NAP1 or Chz1 to either facilitate H2A-H2B dimer removal or deliver the variant histone complex [58].…”

Nuclear insulin receptor substrate-1 activates promoters of cell cycle progression genes

“…IRS-1 has no DNA-binding motifs, and it is not a kinase (from the database). Angelov et al (2006) have reported that nucleolin is a histone chaperone that facilitates transcription through the nucleosome. IRS-1, which interacts with many proteins , may work in the same way as nucleolin in facilitating transcription.…”