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| Status |
Public on Jul 29, 2024 |
| Title |
Cohesin trajectories shape the epigenetic and transcriptional landscape of clustered Protocadherin genes for single neuron identities |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
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| Summary |
Cellular individuality is often achieved by stochastic expression of single genes within tandemly-arrayed gene families. This principle is epitomized by the stochastic choice of clustered Protocadherin (Pcdh) genes which generates the extraordinary cell-surface diversity required for neural circuit assembly during development. However, the molecular mechanisms by which this diversity arises are not fully understood. Here, we show that stochastic Pcdh gene choice requires “escape” from silent heterochromatin by a distal transcriptional enhancer. These enhancer/promoter encounters, that lead to promoter derepression, are catalyzed by cohesin, whose processivity, density and stalling at boundaries define the probability of choice of Pcdh genes by determining the probability of enhancer/promoter contacts in mouse olfactory sensory and cortical neurons. We propose that coupling between an epigenetic switch and the modularity of cohesin trajectories allows for different Pcdh profiles to arise across neuronal cell-types, underlying the diversities of their morphologies and functions in the nervous system. More broadly these principles add a layer of regulatory finesse for the generation of transcription diversity from genes arranged in clusters.
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| Overall design |
Examination of single-cell and bulk RNA, CTCF/Cohesin localization on chromatin, genome folding and DNA methylation levels within the clustered Protocadherin locus in olfactory sensory neurons and cortical neurons from mice carrying genetic mutations.
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| Contributor(s) |
Kiefer L, Gaudin S, Rajkumar SM, Servito GF, Langen J, Mui MH, Nawsheen S, Canzio D |
| Citation(s) |
39052779 |
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| Submission date |
Dec 05, 2023 |
| Last update date |
Jul 30, 2024 |
| Contact name |
Lea Kiefer |
| E-mail(s) |
lea.kiefer@ucsf.edu
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| Organization name |
UCSF
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| Street address |
1651 4th Street, Weill Neurosci RM 471A
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| City |
SAN FRANCISCO |
| State/province |
CA |
| ZIP/Postal code |
94103 |
| Country |
USA |
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| Platforms (3) |
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| Samples (80)
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| Relations |
| BioProject |
PRJNA1049022 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE249430_RAW.tar |
30.4 Gb |
(http)(custom) |
TAR (of BEDGRAPH, BW, H5, HIC) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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