Lhx2, Ldb1, and Ebf1 bind Olfactory Receptor gene and intergenic olfactory enhancers

Stable Identifier
R-MMU-9753028
Type
Reaction [binding]
Species
Mus musculus
Compartment
ReviewStatus
5/5
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Lhx2, Ldb1, and Ebf1 bind Olfactory Receptor gene and intergenic olfactory enhancers
Transcription factors Lhx2 and Ebf1 and scaffold protein Ldb1 bind enhancers located between olfactory receptor (OR) genes (Zhang et al. 2016, Monahan et al. 2019). OR genes are initially heterochromatic during development of the olfactory sensory neuron (OSN) lineage (McClintock et al. 2020). A few OR genes become weakly active and then one of these genes becomes highly active while all other OR genes are repressed by heterochromatin. In this way each OSN expresses only one OR gene. The single expressed OR gene is activated by a suprachromosomal cluster of intergenic olfactory enhancers located on the same chromosome and on other chromosomes (Monahan et al. 2017, Monahan et al. 2019). Three dimension analysis of chromatin indicates 8-12 intergenic enhancers are sufficient to activate an OR gene (Tan et al. 2018). Each intergenic olfactory enhancer is bound by the transcription factors Lhx2 and Ebf1 and by the scaffold protein Ldb1, which may mediate enhancer-enhancer interactions (Zhang et al. 2016, Monahan et al. 2017, Monahan et al. 2019). As the expressed OR protein accumulates in the endoplasmic reticulum membrane, it activates the unfolded protein response, which activates translation of Adcy3 that downregulates Kdm1a (Lsd) histone methyltransferase (Dalton et al. 2013, Lyons et al. 2014). The downregulation of Kdm1a prevents any other OR genes from becoming active. Kdm1a is required for maturation of OSNs (Coleman et al. 2017)
Literature References
PubMed ID Title Journal Year
28933695 Cooperative interactions enable singular olfactory receptor expression in mouse olfactory neurons

Lomvardas, S, Monuki, ES, Monahan, K, Mumbey-Wafula, A, Schieren, I, Cheung, J

Elife 2017
30626972 LHX2- and LDB1-mediated trans interactions regulate olfactory receptor choice

Horta, A, Lomvardas, S, Monahan, K

Nature 2019
30936528 Three-dimensional genome structures of single sensory neurons in mouse visual and olfactory systems

Daley, N, Xing, D, Xie, XS, Tan, L

Nat Struct Mol Biol 2019
27822500 Lhx2 Determines Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons

Zhang, G, McClintock, TS, Stromberg, AJ, Biecker, SM, Titlow, WB

eNeuro 2016
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