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LHX2- and LDB1-mediated trans interactions regulate olfactory receptor choice

Author

Listed:
  • Kevin Monahan

    (Columbia University)

  • Adan Horta

    (Columbia University)

  • Stavros Lomvardas

    (Columbia University
    Columbia University
    Columbia University)

Abstract

The genome is partitioned into topologically associated domains and genomic compartments with shared chromatin valence. This architecture is constrained by the DNA polymer, which precludes interactions between genes on different chromosomes. Here we report a marked divergence from this pattern of nuclear organization that occurs in mouse olfactory sensory neurons. Chromatin conformation capture using in situ Hi-C on fluorescence-activated cell-sorted olfactory sensory neurons and their progenitors shows that olfactory receptor gene clusters from 18 chromosomes make specific and robust interchromosomal contacts that increase with differentiation of the cells. These contacts are orchestrated by intergenic olfactory receptor enhancers, the ‘Greek islands’, which first contribute to the formation of olfactory receptor compartments and then form a multi-chromosomal super-enhancer that associates with the single active olfactory receptor gene. The Greek-island-bound transcription factor LHX2 and adaptor protein LDB1 regulate the assembly and maintenance of olfactory receptor compartments, Greek island hubs and olfactory receptor transcription, providing mechanistic insights into and functional support for the role of trans interactions in gene expression.

Suggested Citation

  • Kevin Monahan & Adan Horta & Stavros Lomvardas, 2019. "LHX2- and LDB1-mediated trans interactions regulate olfactory receptor choice," Nature, Nature, vol. 565(7740), pages 448-453, January.
  • Handle: RePEc:nat:nature:v:565:y:2019:i:7740:d:10.1038_s41586-018-0845-0
    DOI: 10.1038/s41586-018-0845-0
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    Cited by:

    1. François Serra & Andrea Nieto-Aliseda & Lucía Fanlo-Escudero & Llorenç Rovirosa & Mónica Cabrera-Pasadas & Aleksey Lazarenkov & Blanca Urmeneta & Alvaro Alcalde-Merino & Emanuele M. Nola & Andrei L. O, 2024. "p53 rapidly restructures 3D chromatin organization to trigger a transcriptional response," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Sandhya Chandrasekaran & Sergio Espeso-Gil & Yong-Hwee Eddie Loh & Behnam Javidfar & Bibi Kassim & Yueyan Zhu & Yuan Zhang & Yuhao Dong & Lucy K. Bicks & Haixin Li & Prashanth Rajarajan & Cyril J. Pet, 2021. "Neuron-specific chromosomal megadomain organization is adaptive to recent retrotransposon expansions," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    3. Ziad Ibrahim & Tao Wang & Olivier Destaing & Nicola Salvi & Naghmeh Hoghoughi & Clovis Chabert & Alexandra Rusu & Jinjun Gao & Leonardo Feletto & Nicolas Reynoird & Thomas Schalch & Yingming Zhao & Ma, 2022. "Structural insights into p300 regulation and acetylation-dependent genome organisation," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
    4. Joana R. C. Faria & Michele Tinti & Catarina A. Marques & Martin Zoltner & Harunori Yoshikawa & Mark C. Field & David Horn, 2023. "An allele-selective inter-chromosomal protein bridge supports monogenic antigen expression in the African trypanosome," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    5. Nimrod Rappoport & Elad Chomsky & Takashi Nagano & Charlie Seibert & Yaniv Lubling & Yael Baran & Aviezer Lifshitz & Wing Leung & Zohar Mukamel & Ron Shamir & Peter Fraser & Amos Tanay, 2023. "Single cell Hi-C identifies plastic chromosome conformations underlying the gastrulation enhancer landscape," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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