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| Status |
Public on Feb 23, 2018 |
| Title |
Ubiquitin C-terminal hydrolase isozyme L1 (UCHL1) is associated with shelterin complex at interstitial telomeric sites |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Ubiquitin C-terminal hydrolase isozyme L1 (UCHL1) is primarily expressed in neuronal cells and neuroendocrine cells. It is a multifunctional protein involved in deubiquitination, ubiquitination, and ubiquitin homeostasis. UCHL1 has been associated with various diseases, including many cancers, but its specific roles are disputed and still generally undetermined. Herein, we demonstrate that UCHL1 is associated with genomic DNA in certain prostate cancer cell lines, including DU 145 cells derived from a brain metastatic site, and in HEK293T embryonic kidney cells with a neuronal lineage. Chromatin immunoprecipitation and sequencing revealed that UCHL1 localizes to TTAGGG repeats at telomeres and interstitial telomeric sequences, as do TRF1 and TRF2, components of the shelterin complex. A weak or transient interaction between UCHL1 and the shelterin complex was confirmed by immunoprecipitation and proximity ligation assays. UCHL1 and TERF2IP, also a component of the shelterin complex, were bound to the nuclear scaffold. UCHL1 may play a role in regulating gene expression by affecting the stabilization of the shelterin proteins or influencing nuclear targeting. As several shelterin proteins (TRF1, TRF2, POT1 and TERF2IP) are ubiquitinated, UCHL1 may have a role in regulating the stability of these proteins. UCHL1 may also regulate the nuclear location of shelterin-associated genomic regions.
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| Overall design |
A total of six samples were analyzed in the examination of genomic distribution of UCHL1 in DU 145 and HEK293T cells. Firstly, UCHL1 ChIP seq was performed in DU 145 1% formaldehyde cross-linked cells. Then, UCHL1 ChIP seq was performed in dual cross-linked (1mM DSP and 1% formaldehyde) DU 145 and HEK293T cells. All three UCHL1 ChIP seq samples were analyzed compared to their respective DNA inputs.
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| Contributor(s) |
Ilic A, Lu S, Bhatia V, Begum F, Klonisch T, Agarwal P, Xu W, Davie JR |
| Citation(s) |
29126443 |
| Submission date |
Mar 28, 2017 |
| Last update date |
Jan 16, 2023 |
| Contact name |
James Ronald Davie |
| E-mail(s) |
jim.davie@umanitoba.ca
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| Phone |
2042723174
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| Organization name |
University of Manitoba
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| Department |
Biochemistry and Medical Genetics
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| Street address |
745 Bannatyne Avenue, RM 333A
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| City |
Winnipeg |
| State/province |
Manitoba |
| ZIP/Postal code |
R3E 0J9 |
| Country |
Canada |
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| Platforms (1) |
| GPL16288 |
AB 5500xl Genetic Analyzer (Homo sapiens) |
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| Samples (6)
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| GSM2551854 |
Input DNA of DU 145 (cross-linking with 1% formaldehyde) |
| GSM2551855 |
UCHL1 ChIP DNA of DU 145 (cross-linking with 1% formaldehyde) |
| GSM2551856 |
Input DNA of DU 145 (cross-linking with 1mM DSP and 1% formaldehyde) |
| GSM2551857 |
UCHL1 ChIP DNA of DU 145 (cross-linking with 1mM DSP and 1% formaldehyde) |
| GSM2551858 |
Input DNA of HEK293T (cross-linking with 1mM DSP and 1% formaldehyde) |
| GSM2551859 |
UCHL1 ChIP DNA of HEK293T (cross-linking with 1mM DSP and 1% formaldehyde) |
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| Relations |
| BioProject |
PRJNA380736 |
| SRA |
SRP102576 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE97111_RAW.tar |
130.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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