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| Status |
Public on Apr 21, 2022 |
| Title |
The FACT complex facilitates expression of lysosomal and antioxidant genes through binding to TFEB and TFE3 [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The transcription factors TFEB and TFE3 orchestrate the cellular response to a variety of stressors, including nutrient deprivation, oxidative stress, and pathogens. Here we describe a novel interaction between TFEB/TFE3 and FACT, a heterodimeric histone chaperone consisting of SSRP1 and SPT16 that mediates nucleosome disassembly and assembly, thus facilitating transcription. Extracellular stimuli, such as nutrient deprivation or oxidative stress, induce nuclear translocation and activation of TFEB and TFE3, which then associate with the FACT complex to regulate stress-induced gene transcription. Depletion of FACT does not affect TFEB activation, stability, or binding to the promoter of target genes. In contrast, reduction of FACT levels by siRNA or treatment with the FACT inhibitor curaxin, severely impair induction of numerous antioxidant and lysosomal genes, revealing a crucial role of FACT as a regulator of cellular homeostasis. Furthermore, upregulation of antioxidant genes induced by TFEB over-expression is significantly reduced by curaxin, consistent with a role of FACT as a TFEB transcriptional activator. Together, our data show that chromatin remodeling at the promoter of stress-responsive genes by FACT is important for efficient expression of TFEB/TFE3 targets, thus providing a link between environmental changes, chromatin modifications and transcriptional regulation.
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| Overall design |
Analysis of mRNA expression under different stress conditions in HeLa cells depleted of FACT complex.
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| Contributor(s) |
Jeong E, Martina JA, Contreras PS, Puertollano R |
| Citation(s) |
35230915 |
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| Submission date |
Jul 18, 2021 |
| Last update date |
Apr 21, 2022 |
| Contact name |
Jose Martina |
| E-mail(s) |
[email protected]
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| Organization name |
NIH
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| Department |
NHLBI, CDBC
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| Lab |
LCB
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| Street address |
50 South Dr., Building 50, Room 3533
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| City |
Bethesda |
| State/province |
Maryland |
| ZIP/Postal code |
20892-8018 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE180324 |
The FACT complex facilitates expression of lysosomal and antioxidant genes through binding to TFEB and TFE3. |
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| Relations |
| BioProject |
PRJNA747826 |
| SRA |
SRP328843 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE180323_DESeq2_results_allgenes.xlsx |
5.0 Mb |
(ftp)(http) |
XLSX |
| GSE180323_Raw_gene_counts_matrix.txt.gz |
2.4 Mb |
(ftp)(http) |
TXT |
| GSE180323_gene_matrix_fpkm.txt.gz |
2.9 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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