Presentation Details
| Tex15 as a marker of transient multi-ORs expression in developing olfactory neurons Kaitao Zhao, Nusrath Yusuf, Joshua Danoff, Kevin Monahan. Rutgers University, PISCATAWAY, NJ, USA |
Abstract
Before establishing singular odorant receptor (OR) expression, olfactory sensory neurons (OSNs) pass through a transient developmental stage in which multiple OR genes are co-expressed within individual cells. The regulatory mechanisms that permit this temporary co-expression remain elusive. Here, we show that this developmental window is associated with a markedly more accessible chromatin state across OR gene clusters, accompanied by binding of key OR transcription factors to many more sites. To interrogate this stage, we generated a new Tex15CreER allele that enables inducible labeling of early OSN progenitors committed to the neuronal lineage but prior to activation of immature neuronal markers such as Ngn-GFP. RNA-seq analysis confirms that this allele labels a population corresponding to immediate neuronal progenitors (INPS), the stage at which OR gene co-expression occurs. ATAC-seq profiling of Tex15CreER labeled cells reveals stage specific chromatin accessibility, including hundreds of sites within OR gene clusters that are significantly more accessible than in mature OSNs. Consistent with this, Lhx2 and Ldb1 transcription factors that regulate OR gene expression occupy many additional binding sites in immature cells. In contrast, Greek Island enhancer elements display a distinct temporal pattern, with weak accessibility in Tex15CreER cells, peak accessibility in Ngn-GFP cells, and reduced accessibility again in mature OSNs. Together, these results indicate that OR gene clusters undergo dynamic chromatin remodeling during OSN differentiation, enabling transient multi-OR expression before the establishment of 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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