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| Status |
Public on Nov 28, 2024 |
| Title |
Motif distribution and DNA methylation underlie distinct Cdx2 binding during development and homeostasis |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Other
|
| Summary |
Transcription factors guide tissue development by binding to developmental stage-specific targets and establishing an appropriate enhancer landscape. In turn, DNA and chromatin modifications direct the genomic binding of transcription factors. However, how transcription factors navigate chromatin features to selectively bind a small subset of all the possible genomic target loci remains poorly understood. Here we show that Cdx2 - a lineage defining transcription factor that binds distinct targets in developing versus adult intestinal epithelial cells - has a preferential affinity for a non-canonical CpG-containing motif in vivo. A higher frequency of this motif at embryonic Cdx2 targets and methylated state of the CpG during development enables selective Cdx2 binding and activation of developmental enhancers and genes. In adult cells, demethylation at these enhancers prevents ectopic Cdx2 binding, instead directing Cdx2 to its canonical motif without a CpG. This shift in Cdx2 binding facilitates Ctcf and Hnf4 recruitment, establishing super-enhancers during development and homeostatic enhancers in adult cells, respectively. Induced DNA methylation in adult mouse epithelium or cultured cells recruits Cdx2 to developmental targets, promoting corecruitment of partner transcription factors. Thus, Cdx2’s differential CpG motif preferences enable it to navigate distinct DNA methylation profiles, activating genes specific to appropriate developmental stages.
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| Overall design |
Refer to individual Series
|
| |
|
| Contributor(s) |
Lorzadeh A, Ye G, Sharma S, Jadhav U |
| Citation missing |
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| |
| Submission date |
Jan 19, 2024 |
| Last update date |
Nov 28, 2024 |
| Contact name |
Unmesh Jadhav |
| E-mail(s) |
[email protected]
|
| Phone |
323-442-2563
|
| Organization name |
University of Southern California
|
| Department |
Stem Cell and Regenerative Medicine
|
| Lab |
Jadhav Lab
|
| Street address |
1425 San Pablo Street
|
| City |
Los Angeles |
| State/province |
California |
| ZIP/Postal code |
90033 |
| Country |
USA |
| |
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| Platforms (3) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (43)
|
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| Relations |
| BioProject |
PRJNA1066827 |
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