Histone H3 is speci®cally phosphorylated during both mitosis and meiosis in patterns that are speci®cally coordinated in both space and time. Histone H3 phosphorylation may initiate at dierent phases of the cell division in dierent organisms, but metaphase chromosomes are always found to be heavily phosphorylated. Upon exit of mitosis/meiosis a global dephosphorylation of H3 takes place. Potential candidates for H3 kinases are described and their hypothetical mechanism of action on highly condensed chromatin templates is discussed. In addition, a novel hypothesis for the role of histone H3 phosphorylation during cell division is proposed. This hypothesis, termed the`ready production label' model, explains the results in the literature and suggests that phosphorylation of histone H3 is a part of a complex signaling mechanism. Oncogene (2001) 20, 3021 ± 3027.

The unusual histone variant macroH2A (mH2A) has been associated with repression of transcription, but the molecular mechanisms by which it exerts this function are unknown. Here we have identified a mechanism by which the different domains of mH2A may be involved in the repression of transcription. Evidence is presented that the presence of mH2A in a positioned nucleosome interferes with the binding of the transcription factor NF-kappaB. The nonhistone region of mH2A was identified to be associated with this interference. Importantly, the presence of macroH2A was found to severely impede SWI/SNF nucleosome remodeling and movement to neighboring DNA segments. This property of mH2A was demonstrated to reside only in its H2A-like domain. A hypothesis explaining the role of histone variants in transcriptional regulation is proposed.

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.