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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 21, 2024 |
| Title |
Global profiling of Nkx2.2 SD-domain mutant pancreas during development and adulthood compared to transcriptional profiling of SD-domain mutant expressing neural progenitors. |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
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| Summary |
The consolidation of unambiguous cell fate commitment relies on the ability of transcription factors (TFs) to exert tissue-specific regulation of complex genetic networks. The mechanisms by which TFs establish such precise control over gene expression, however, have remained elusive—especially in instances where a single TF operates in two or more discrete cellular systems. In this study, we demonstrate that cell specific functions of NKX2.2 are driven by the highly conserved NK2-Specific Domain (SD). Mutation of the endogenous NKX2.2 SD domain prevents the developmental progression of beta cell precursors into mature, insulin-expressing beta cells, resulting in overt neonatal diabetes. Within the adult beta cell, the SD domain stimulates beta cell performance through the activation and repression of a subset of NKX2.2-regulated transcripts critical for beta cell function. These irregularities in beta cell gene expression may be mediated via SD domain-contingent interactions with components of the nuclear pore complex. In stark contrast to these pancreatic phenotypes, however, the SD domain is entirely dispensable for the development of NKX2.2-dependent cell types within the CNS. Together, these results reveal a previously undetermined mechanism through which NKX2.2 directs disparate transcriptional programs in the pancreas vs. neuroepithelium.
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| Overall design |
Examination of total RNA profiles of E15.5 pancreata of wildtype and Nkx2.2SDmut animals, of wildtype and beta-specific Nkx2.2SDmut adult islets, and of mouse ES cell-derived spinal motor neuron progenitors expressing a wildtype copy of Nkx2.2 tagged by FLAG under the control of a doxycycline (DOX) inducible promotor (iNkx2.2), an SD-domain mutant copy of Nkx2.2 tagged by FLAG under the control of a doxycycline (DOX) inducible promotor (iSDmut), or no Nkx2.2 (pMN). Examination of the global DNA binding profile of Nkx2.2 in MIN6 cells. 2-4 replicates are provided for all samples.
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| Contributor(s) |
Abarinov V, Levine JA, Churchill AJ, Hopwood B, Dieter C, Guney MA, Wells KL, Friel JM, Guo Y, Hammelman J, Gifford DK, Magnuson MA, Wichterle H, Sussel L |
| Citation(s) |
37364986 |
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| Submission date |
Feb 28, 2023 |
| Last update date |
May 22, 2024 |
| Contact name |
Elena Abarinov |
| E-mail(s) |
elenavabarinov@gmail.com
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| Organization name |
University of Colorado at Denver
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| Street address |
1775 Aurora Ct
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| City |
Aurora |
| State/province |
Colorado |
| ZIP/Postal code |
80045 |
| Country |
USA |
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| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (27)
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| GSM7073682 |
pMN_EA1_GTTTCG_L002_R1_001 [pMN_CTRL_1] |
| GSM7073683 |
pMN_EA5_ATTCCT_L002_R1_001 [pMN_CTRL_2] |
| GSM7073684 |
pMN_EA13_ACTGAT_L004_R1_001 [pMN_CTRL_3] |
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| Relations |
| BioProject |
PRJNA939831 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE226345_Adult_pancreas_FPKM.txt.gz |
664.3 Kb |
(ftp)(http) |
TXT |
| GSE226345_Adult_pancreas_RNAseq_SDmut_vs_CTRL_SigGenes.txt.gz |
438.0 Kb |
(ftp)(http) |
TXT |
| GSE226345_Adult_pancreas_RNAseq_readcounts.txt.gz |
362.9 Kb |
(ftp)(http) |
TXT |
| GSE226345_E15.5_pancreas_RNAseq_Normalized_readcounts.txt.gz |
932.6 Kb |
(ftp)(http) |
TXT |
| GSE226345_E15.5_pancreas_RNAseq_SigGenes.txt.gz |
690.5 Kb |
(ftp)(http) |
TXT |
| GSE226345_E15.5_pancreas_RNAseq_readcounts.txt.gz |
772.5 Kb |
(ftp)(http) |
TXT |
| GSE226345_Neural_progenitors_RNAseq_FPKM.txt.gz |
726.1 Kb |
(ftp)(http) |
TXT |
| GSE226345_Neural_progenitors_RNAseq_SigGenes.txt.gz |
83.2 Kb |
(ftp)(http) |
TXT |
| GSE226345_Neural_progenitors_RNAseq_readcounts.txt.gz |
440.8 Kb |
(ftp)(http) |
TXT |
| GSE226345_Nkx2.2_logCPM_final_sites.txt.gz |
64.3 Kb |
(ftp)(http) |
TXT |
| GSE226345_RawCounts_Nkx2.2_all_GEM_events.txt.gz |
82.0 Kb |
(ftp)(http) |
TXT |
| GSE226345_betaSDmut_vs_betaKO_Nkx2.2_bound_SigGenes.txt.gz |
227.3 Kb |
(ftp)(http) |
TXT |
| GSE226345_betaSDmut_vs_betaKO_vs_CTRL_SigGenes.txt.gz |
696.8 Kb |
(ftp)(http) |
TXT |
| GSE226345_readme.txt |
1.5 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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