Presentation Details
| Don Tucker Finalist: Tex15 controls runaway olfactory receptor transcription to necessitate diverse olfactory receptor choice Nusrath Yusuf1, Jerome Kahiapo1, David Brann3, Alina Irvine2, Josh Danoff1, Silas Sun1, Nader Boutros-Ghali1, Paige Kramer1, Sandeep Datta3, Jackie Yang1, Kevin Monahan1. 1Rutgers University, Highland Park, NJ, USA.2Swarthmore College, Swarthmore, PA, USA.3Havard Medical School, Boston, MA, USA |
Abstract
Hundreds of different types of odorant receptors (ORs) are expressed by olfactory sensory neurons (OSNs) in the mouse olfactory epithelium (MOE), but each OSN expresses only one allele of one of OR gene. The choice of a single OR gene occurs as neuronal progenitors differentiate and is accompanied by widespread changes at OR gene loci. How these processes interact to effectuate diverse but singular OR across all OSNs remains poorly understood. We show that Testes expressed gene 15 (Tex15) is transiently expressed by OSN progenitors and that it is required for generating a diverse population of OSNs subtypes. Mice bearing a Tex15 null allele have reduced H3K9me3 deposition over OR clusters. This is accompanied by a dramatic reduction in OSN diversity, with OR choice dramatically skewed towards OR genes that are normally expressed at the early stages of differentiation and then repressed. Tex15 KO mice fail to repress these ORs and generally exhibit increased levels of OR transcription in OSN progenitors. These early expressed OR genes preferentially assemble into the Greek Island enhancer hubs that control OR gene choice. This breakdown of the normal choice process is accompanied by a disruption of the spatial patterning of OR gene expression, where upregulated OR genes predominate in the ventral MOE. These findings reveal a novel mechanism that represses the expression of the earliest expressed OR genes, allowing OR choice to sample the full repertoire of OR genes. In the absence of this mechanism early transcription of OR genes result in a deterministic pattern of OR gene selection leading to a few ORs getting highly expressed. Taken together these results establish that the regulation of OR transcription in progenitor cells is central to the mechanism that leads to diverse but singular OR choice.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.
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