PT  - JOURNAL ARTICLE
AU  - Elizaveta Bashkirova
AU  - Kevin Monahan
AU  - Christine E. Campbell
AU  - Jason M. Osinski
AU  - Longzhi Tan
AU  - Ira Schieren
AU  - Gilad Barnea
AU  - X. Sunnie Xie
AU  - Richard M. Gronostajski
AU  - Stavros Lomvardas
TI  - Homeotic Regulation of Olfactory Receptor Choice via NFI-dependent Heterochromatic Silencing and Genomic Compartmentalization
AID  - 10.1101/2020.08.30.274035
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.08.30.274035
4099  - http://biorxiv.org/content/early/2020/09/28/2020.08.30.274035.short
4100  - http://biorxiv.org/content/early/2020/09/28/2020.08.30.274035.full
AB  - Expression of one out of >1000 olfactory receptor (OR) genes is stochastic but, yet, spatially organized in stereotypic anatomical segments, or “zones”, along the dorsoventral axis of the mouse olfactory epithelium. We discovered that zonal OR expression is specified by OR chromatin structure and genome architecture during olfactory neuron differentiation. Specifically, across every zone dorsally expressed ORs have higher levels of heterochromatic marks and long-range contacts than ORs expressed ventrally. However, OR heterochromatin levels and frequency of genomic contacts between ORs gradually increase towards ventral zones. Consequently, ORs from dorsal indexes accumulate high H3K9me3/H3K79me3 enrichment and become silenced in ventral zones, while ORs from ventral indexes lack activating long-range genomic interactions and, thus, cannot be chosen in dorsal segments. This process is regulated by NFIA, B, and X gradients along the dorsoventral axis, triple deletion of which causes homeotic transformations on zonal OR expression, heterochromatin formation, and genomic compartmentalization.Competing Interest StatementThe authors have declared no competing interest.