Olfactory expression of trace amine-associated receptors requires cooperative cis-acting enhancers

Ami Shah; Madison Ratkowski; Alessandro Rosa; Paul Feinstein; Thomas Bozza

doi:10.1038/s41467-021-23824-3

Olfactory expression of trace amine-associated receptors requires cooperative cis-acting enhancers

Ami Shah, Madison Ratkowski, Alessandro Rosa, Paul Feinstein, Thomas Bozza^*

^*Corresponding author for this work

Neurobiology

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Olfactory sensory neurons express a large family of odorant receptors (ORs) and a small family of trace amine-associated receptors (TAARs). While both families are subject to so-called singular expression (expression of one allele of one gene), the mechanisms underlying TAAR gene choice remain obscure. Here, we report the identification of two conserved sequence elements in the mouse TAAR cluster (T-elements) that are required for TAAR gene expression. We observed that cell-type-specific expression of a TAAR-derived transgene required either T-element. Moreover, deleting either element reduced or abolished expression of a subset of TAAR genes, while deleting both elements abolished olfactory expression of all TAARs in cis with the mutation. The T-elements exhibit several features of known OR enhancers but also contain highly conserved, unique sequence motifs. Our data demonstrate that TAAR gene expression requires two cooperative cis-acting enhancers and suggest that ORs and TAARs share similar mechanisms of singular expression.

Original language	English (US)
Article number	3797
Journal	Nature communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-23824-3
State	Published - Dec 1 2021

Funding

This work was supported by grants from NIH/NIDCD to A.S (F32DC015962) and T.B. (R01DC013576), and from Northwestern University to M.R. (Office for Undergraduate Research). P.F is supported by R21GM126304 and A.R. is supported by the Research Initiative for Scientific Enhancement (RISE) program at Hunter College, funded by NIH grant GM060665. We thank Sarah Kaye, Hardik Patel, and Amanda Menzie for technical support, Bill Kath for advice on bioinformatics, Lynn Doglio and the Transgenesis and Targeted Mutagenesis Laboratory at Northwestern University for production of transgenic mice, and Pieter Faber and the Genomics Facility at University of Chicago for high-throughput sequencing. We are indebted to Tom Meade and Hao Li in the Department of Chemistry at Northwestern for synthesis of HNPP.

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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abstract = "Olfactory sensory neurons express a large family of odorant receptors (ORs) and a small family of trace amine-associated receptors (TAARs). While both families are subject to so-called singular expression (expression of one allele of one gene), the mechanisms underlying TAAR gene choice remain obscure. Here, we report the identification of two conserved sequence elements in the mouse TAAR cluster (T-elements) that are required for TAAR gene expression. We observed that cell-type-specific expression of a TAAR-derived transgene required either T-element. Moreover, deleting either element reduced or abolished expression of a subset of TAAR genes, while deleting both elements abolished olfactory expression of all TAARs in cis with the mutation. The T-elements exhibit several features of known OR enhancers but also contain highly conserved, unique sequence motifs. Our data demonstrate that TAAR gene expression requires two cooperative cis-acting enhancers and suggest that ORs and TAARs share similar mechanisms of singular expression.",

author = "Ami Shah and Madison Ratkowski and Alessandro Rosa and Paul Feinstein and Thomas Bozza",

note = "Funding Information: This work was supported by grants from NIH/NIDCD to A.S (F32DC015962) and T.B. (R01DC013576), and from Northwestern University to M.R. (Office for Undergraduate Research). P.F is supported by R21GM126304 and A.R. is supported by the Research Initiative for Scientific Enhancement (RISE) program at Hunter College, funded by NIH grant GM060665. We thank Sarah Kaye, Hardik Patel, and Amanda Menzie for technical support, Bill Kath for advice on bioinformatics, Lynn Doglio and the Transgenesis and Targeted Mutagenesis Laboratory at Northwestern University for production of transgenic mice, and Pieter Faber and the Genomics Facility at University of Chicago for high-throughput sequencing. We are indebted to Tom Meade and Hao Li in the Department of Chemistry at Northwestern for synthesis of HNPP. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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N2 - Olfactory sensory neurons express a large family of odorant receptors (ORs) and a small family of trace amine-associated receptors (TAARs). While both families are subject to so-called singular expression (expression of one allele of one gene), the mechanisms underlying TAAR gene choice remain obscure. Here, we report the identification of two conserved sequence elements in the mouse TAAR cluster (T-elements) that are required for TAAR gene expression. We observed that cell-type-specific expression of a TAAR-derived transgene required either T-element. Moreover, deleting either element reduced or abolished expression of a subset of TAAR genes, while deleting both elements abolished olfactory expression of all TAARs in cis with the mutation. The T-elements exhibit several features of known OR enhancers but also contain highly conserved, unique sequence motifs. Our data demonstrate that TAAR gene expression requires two cooperative cis-acting enhancers and suggest that ORs and TAARs share similar mechanisms of singular expression.

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Olfactory expression of trace amine-associated receptors requires cooperative cis-acting enhancers

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