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| Status |
Public on Apr 29, 2019 |
| Title |
TET enzymes augment AID expression via 5hmC modifications at the Aicda superenhancer [BS-seq] |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
TET enzymes are dioxygenases that promote DNA demethylation by oxidizing the methyl group of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Here we report a close correspondence between 5hmC-marked regions, chromatin accessibility and enhancer activity in B cells, and a strong enrichment for consensus binding motifs for basic region-leucine zipper (bZIP) transcription factors at TET-responsive genomic regions. Functionally, Tet2 and Tet3 regulate class switch recombination (CSR) in murine B cells by enhancing expression of Aicda, encoding the cytidine deaminase AID essential for CSR. TET enzymes deposit 5hmC, demethylate and maintain chromatin accessibility at two TET-responsive elements, TetE1 and TetE2, located within a superenhancer in the Aicda locus. Transcriptional profiling identified BATF as the bZIP transcription factor involved in TET-dependent Aicda expression. 5hmC is not deposited at TetE1 in activated Batf-deficient B cells, indicating that BATF recruits TET proteins to the Aicda enhancer. Our data emphasize the importance of TET enzymes for bolstering AID expression, and highlight 5hmC as an epigenetic mark that captures enhancer dynamics during cell activation.
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| Overall design |
5hmC mapping by CMS-IP, ATAC-seq, RNA-seq, ChIP-seqs using B cells unstimulated or activated as a function time. Cells were either from WT or with Tet2/3 acutely deleted.
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| Contributor(s) |
Lio CJ, Shukla V, Gonzalez-Avalos E, Samaniego-Castruita D, Chakraborty A, Yue X, Schatz DG, Ay F, Rao A |
| Citation(s) |
31028100 |
| |
| Submission date |
Jun 25, 2018 |
| Last update date |
May 29, 2019 |
| Contact name |
Anjana Rao |
| E-mail(s) |
arao@lji.org
|
| Organization name |
La Jolla Institute for Allergy and Immunology
|
| Department |
Signaling and Gene Expression
|
| Lab |
Anjana Rao
|
| Street address |
9420 Athena Cir
|
| City |
La Jolla |
| State/province |
California |
| ZIP/Postal code |
92037 |
| Country |
USA |
| |
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| Platforms (1) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE116208 |
TET enzymes augment AID expression via 5hmC modifications at the Aicda superenhancer |
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| Relations |
| BioProject |
PRJNA477775 |
| SRA |
SRP151240 |
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