Paircounting

Abstract

X inactivation presents two longstanding puzzles: the counting and choice of X chromosomes. Here, we consider counting and choice in the context of pairing, both of the X and of the autosomes.

Keywords: X inactivation; X, autosomes; choice; counting; pairing.

Figure 1.. Paircounting.

(A) Homolog pairing reduces the number of entities to be counted by half. Autosomes are shown in gray and X chromosomes in black. (B) Once singularity has been generated by pairing, binding of that singularity by one copy of a factor (red circle) that then impacts, marks, or persists on just one of the two allelic regions will necessarily result in allelic distinction. Given that there is only a single binding site for the factor, the proposed mechanism could achieve allelic distinction regardless of how many copies of the factor are in the nucleus. As for the nature of the factor and its subsequent mark, many forms are possible, including protein, nucleic acid, epigenetic, structural, and/or combinations thereof. (C, D) In these hypothetical cells carrying three pairs of autosomes and either two (C) or three (D) X chromosomes, X inactivation begins with paircounting of the autosomes and the generation of singularities; here, we show one paircounted region per chromosome, although there could be more, followed by the binding of each paired region by a factor (colored circles), aggregation of the factors into a singularity, and then selection by the singularity of one X to remain active (Xa), with all other Xs becoming inactive (Xi). Singularity could also be achieved by aggregation of (or sequential interaction between) the paired autosomal regions, themselves. Observations of telomere aggregation would be consistent with the paircounted autosomal regions being telomeric or subtelomeric, one study explicitly tying (sub)telomeric pairing to X inactivation [6].