HP1β and H3K9me3 Regulate Olfactory Receptor Choice and Transcriptional Identity.

Overview

1. Department of Biochemistry and Molecular Biophysics, Mortimer B. Zuckerman Mind Brain and Behavior Institute, Columbia University, New York, NY 10027, USA
2. Department of Anatomy, School of Medicine, University of California San Francisco, San Francisco, CA 94158, USA
3. Lawrence Berkeley National Laboratory, Molecular Biophysics and Integrated Bioimaging Division, Berkeley, CA 94720, USA
4. B24 Beamline, Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK
5. Department of Biological Sciences, Fairchild Center, Columbia University, New York, NY 10027, USA
6. Nelson Biological Laboratories, Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA

Abstract

Diverse epigenetic regulatory mechanisms ensure and modulate cellular diversity. The histone 3 lysine 9 me3 (H3K9me3) post-translational modification participates in silencing lineage-inappropriate genes by restricting access of transcription factors and other regulatory proteins to genes that control cell fate. Mouse olfactory sensory neurons (OSNs) select one olfactory receptor (OR) gene out of 2600 possibilities. This monoallelic and stochastic OR choice occurs as OSNs differentiate and undergo dramatic changes in nuclear architecture. OR genes from different chromosomes converge into specialized nuclear bodies and chromatin compartments, as H3K9me3 and chromatin binding proteins including heterochromatin protein 1 (HP1) are incorporated. In this work, we have uncovered an unexpected role for HP1β in OR choice and neuronal identity that cannot be rescued by HP1α in vivo. With the use of a conditional knock-in mouse model, that after CRE expression replaces HP1β with HP1α, we observe changes in H3K9me3 levels and DNA accessibility over OR gene clusters. These changes alter the expression patterns that partition the mouse olfactory epithelium into five OR expression zones, which results in a reduced OR repertoire that leads to a loss of olfactory sensory neuron diversity. We propose that HP1β modulates the competition of OR promoters for enhancers to promote receptor diversity by establishing repression gradients in a zonal fashion.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• geo:GSE324835, at NCBI GEO; found in “Data Availability Statement”

Data Availability Statement

The original contributions presented in this study are included in the article/Supplementary Materials. Further information and requests for resources and reagents should be directed to the lead contact Martin Escamilla: genomic data are available at Cut & Run (release date 23 March 2026): https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324835; ATAC-Seq (release date 23 March 2026): https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324834; scRNA-seq (release date 23 March 2026): https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324728; ChIP-seq (release date 23 March 2026): https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc= GSE324864 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324864); RNA-seq: (release date 23 March 2026): https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc= GSE325634 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325634); Proteomics (release date 23 March 2026): ftp://massive-ftp.ucsd.edu/v12/MSV000101119/.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 6 keywords, 10 MeSH terms, 2 funders, 104 references.

Cite

This paper

Escamilla-del-Arenal, M., Duffié, R., Shayya, H., Loconte, V., Ekman, A., Street, L., Monahan, K., Larabell, C., Jovanovic, M., & Lomvardas, S. (2026). HP1β and H3K9me3 Regulate Olfactory Receptor Choice and Transcriptional Identity. International journal of molecular sciences, 27(7), 2958. https://doi.org/10.3390/ijms27072958

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