Do the charges matter?-balancing the charges of the chromodomain proteins on the nucleosome

The chromodomain (CD) is a member of the Royal family of conserved chromatin-binding motifs with methylated substrate binding ability, and is often found in 'readers' or 'writers' of repressive histone marks. The regions upstream or downstream of the CD are generally highly charged. Several previous studies suggested that these charged regions modulate the CD's chromatin-binding activity. Considering the relatively weak interaction between the CD and a modified histone tail, it is puzzling how the highly charged CD-flanking regions are 'balanced' on the highly charged nucleosomes to mediate a modification-dependent interaction. Interestingly, the charge distributions along the CD and surrounding regions appear to be distinct among different types of readers and writers, indicating their functional relevance. Here, we describe and discuss the current understanding of the highly charged CD-flanking regions and the potential experimental concerns caused by the regions.