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| Status |
Public on Nov 14, 2018 |
| Title |
SETDB1 compacts the inactive X chromosome in part through silencing an enhancer in the IL1RAPL1 gene |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The product of dosage compensation in human females is the compacted inactive X chromosome (Xi). Here we show that loss of SET domain bifurcated 1 (SETDB1) results in decompaction of the Xi territory coupled with reactivation on the Xi of a powerful enhancer within the 1.4 Mb interleukin-1 receptor accessory protein like 1 (IL1RAPL1) gene at Xp21.2. The enhancer is centrally located in a 0.5 Mb region corresponding to the 3’ third of the IL1RAPL1 locus that transitions from a heterochromatic territory to a euchromatic configuration on the Xi in the absence of SETDB1. This same region showing chromatin instability is part of a common chromosome fragile site that is frequently deleted or rearranged in patients afflicted with intellectual disability and other neurological ailments. Immediately adjacent to the enhancer is an ERVL-MaLR element that drives bi-directional transcription of novel long sense and antisense transcripts. Deletion of the enhancer from the Xa (but not Xi), resulted in detection of bi-directional expression from the Xi coupled with decompaction of the chromosome territory, supporting a critical role for SETDB1 in maintaining this interval in a silent state to facilitate Xi compaction.
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| Overall design |
Examination of three different histone modifications in parental and knock out cells, as well as rRNA-depleted total-RNA-Seq in the parental cells and two independent knock-out clones.
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| Contributor(s) |
Sun Z, Chadwick BP |
| Citation(s) |
30103804 |
| |
| Submission date |
Apr 19, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Brian P Chadwick |
| E-mail(s) |
chadwick@bio.fsu.edu
|
| Phone |
850-645-9279
|
| Organization name |
Florida State University
|
| Department |
Biological Science
|
| Street address |
319 Stadium Drive, King 3076
|
| City |
Tallahassee |
| State/province |
FL |
| ZIP/Postal code |
32306 |
| Country |
USA |
| |
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| Platforms (2) |
| GPL18460 |
Illumina HiSeq 1500 (Homo sapiens) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA451021 |
| SRA |
SRP141213 |
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