MEF2D drives photoreceptor development through a genome-wide competition for tissue-specific enhancers
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA260925 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1574330_1.fastq.gz | Fastqsanger.gz | |||
| SRR1574330_2.fastq.gz | Fastqsanger.gz | |||
| SRR1574490.fastq.gz | Fastqsanger.gz | |||
| SRR1574500.fastq.gz | Fastqsanger.gz | |||
| SRR1574510.fastq.gz | Fastqsanger.gz |
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Project description:Organismal development requires the precise coordination of genetic programs to regulate cell fate and function. MEF2 transcription factors play essential roles in this process but how these broadly expressed factors contribute to the generation of specific cell types during development is poorly understood. Here we show that despite being expressed in virtually all mammalian tissues, in the retina MEF2D binds to retina-specific enhancers and controls photoreceptor cell development. MEF2D achieves specificity by cooperating with a retina-specific factor CRX, which recruits MEF2D away from canonical MEF2 binding sites, and redirects it to retina-specific enhancers that lack the consensus MEF2 sequence. Once bound to retina-specific enhancers, MEF2D and CRX co-activate the expression of photoreceptor-specific genes that are critical for retinal function. These findings demonstrate that broadly expressed TFs acquire specific functions through competitive recruitment to enhancers by tissue-specific TFs, and through cooperative activation of these enhancers to regulate tissue-specific genes.
2015-03-19 | GSE61389 | GEO
Project description:Organismal development requires the precise coordination of genetic programs to regulate cell fate and function. MEF2 transcription factors play essential roles in this process but how these broadly expressed factors contribute to the generation of specific cell types during development is poorly understood. Here we show that despite being expressed in virtually all mammalian tissues, in the retina MEF2D binds to retina-specific enhancers and controls photoreceptor cell development. MEF2D achieves specificity by cooperating with a retina-specific factor CRX, which recruits MEF2D away from canonical MEF2 binding sites, and redirects it to retina-specific enhancers that lack the consensus MEF2 sequence. Once bound to retina-specific enhancers, MEF2D and CRX co-activate the expression of photoreceptor-specific genes that are critical for retinal function. These findings demonstrate that broadly expressed TFs acquire specific functions through competitive recruitment to enhancers by tissue-specific TFs, and through cooperative activation of these enhancers to regulate tissue-specific genes.
2015-03-19 | GSE61391 | GEO
Project description:Organismal development requires the precise coordination of genetic programs to regulate cell fate and function. MEF2 transcription factors (TFs) play essential roles in this process but how these broadly expressed factors contribute to the generation of specific cell types during development is poorly understood. Here we show that despite being expressed in virtually all mammalian tissues, in the retina MEF2D binds to retina-specific enhancers and controls photoreceptor cell development. MEF2D achieves specificity by cooperating with a retina-specific factor CRX, which recruits MEF2D away from canonical MEF2 binding sites and redirects it to retina-specific enhancers that lack the consensus MEF2-binding sequence. Once bound to retina-specific enhancers, MEF2D and CRX co-activate the expression of photoreceptor-specific genes that are critical for retinal function. These findings demonstrate that broadly expressed TFs acquire specific functions through competitive recruitment to enhancers by tissue-specific TFs and through selective activation of these enhancers to regulate tissue-specific genes.
| S-EPMC4393375 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2015-03-19 | GSE61392 | GEO
Project description:MEF2D drives photoreceptor development through a genome-wide competition for tissue-specific enhancers (RNA-Seq)
| PRJNA260926 | ENA
Project description:MEF2D drives photoreceptor development through a genome-wide competition for tissue-specific enhancers (ChIP-Seq)
| PRJNA260927 | ENA
Project description:Acute myeloid leukemia (AML) with MLL-rearrangement (MLL-r) comprises approximately 10% of all AML cases and portends poor outcomes. Much remains to be uncovered on how MLL-r AML drives leukemia development while preventing cells from normal myeloid differentiation. Here, we identified that transcription factor MEF2D is a highly expressed gene with a super-enhancer MLL-r AML. Knockout of MEF2D profoundly impaired leukemia growth, induced myeloid differentiation, and delayed oncogenic progression in vivo. Mechanistically, MEF2D loss led to robust activation of a CEBPE-centered myeloid differentiation program in AML cells. Chromatin profiling revealed that MEF2D binds to and suppresses the chromatin accessibility of CEBPE cis-regulatory regions. In human acute leukemia patient samples, MEF2D expression showed a strong negative correlation with the expression of CEBPE. Depletion of CEBPE partially rescued the cell growth defect and myeloid cell differentiation induced by the loss of MEF2D. Lastly, we show that MEF2D is positively regulated by HOXA9, and downregulation of MEF2D is an important mechanism for DOT1L inhibitor-induced anti-leukemia effects in MLL-r AML. Collectively, our findings suggest that MEF2D plays a critical role in human MLL-r AML and uncover the MEF2D-CEBPE axis as a crucial transcriptional mechanism regulating leukemia cell self-renewal and differentiation block in MLL-r AML.
2021-10-03 | GSE165981 | GEO
Project description:Acute myeloid leukemia (AML) with MLL-rearrangement (MLL-r) comprises approximately 10% of all AML cases and portends poor outcomes. Much remains to be uncovered on how MLL-r AML drives leukemia development while preventing cells from normal myeloid differentiation. Here, we identified that transcription factor MEF2D is a highly expressed gene with a super-enhancer MLL-r AML. Knockout of MEF2D profoundly impaired leukemia growth, induced myeloid differentiation, and delayed oncogenic progression in vivo. Mechanistically, MEF2D loss led to robust activation of a CEBPE-centered myeloid differentiation program in AML cells. Chromatin profiling revealed that MEF2D binds to and suppresses the chromatin accessibility of CEBPE cis-regulatory regions. In human acute leukemia patient samples, MEF2D expression showed a strong negative correlation with the expression of CEBPE. Depletion of CEBPE partially rescued the cell growth defect and myeloid cell differentiation induced by the loss of MEF2D. Lastly, we show that MEF2D is positively regulated by HOXA9, and downregulation of MEF2D is an important mechanism for DOT1L inhibitor-induced anti-leukemia effects in MLL-r AML. Collectively, our findings suggest that MEF2D plays a critical role in human MLL-r AML and uncover the MEF2D-CEBPE axis as a crucial transcriptional mechanism regulating leukemia cell self-renewal and differentiation block in MLL-r AML.
2021-10-02 | GSE165979 | GEO
Project description:Acute myeloid leukemia (AML) with MLL-rearrangement (MLL-r) comprises approximately 10% of all AML cases and portends poor outcomes. Much remains to be uncovered on how MLL-r AML drives leukemia development while preventing cells from normal myeloid differentiation. Here, we identified that transcription factor MEF2D is a highly expressed gene with a super-enhancer MLL-r AML. Knockout of MEF2D profoundly impaired leukemia growth, induced myeloid differentiation, and delayed oncogenic progression in vivo. Mechanistically, MEF2D loss led to robust activation of a CEBPE-centered myeloid differentiation program in AML cells. Chromatin profiling revealed that MEF2D binds to and suppresses the chromatin accessibility of CEBPE cis-regulatory regions. In human acute leukemia patient samples, MEF2D expression showed a strong negative correlation with the expression of CEBPE. Depletion of CEBPE partially rescued the cell growth defect and myeloid cell differentiation induced by the loss of MEF2D. Lastly, we show that MEF2D is positively regulated by HOXA9, and downregulation of MEF2D is an important mechanism for DOT1L inhibitor-induced anti-leukemia effects in MLL-r AML. Collectively, our findings suggest that MEF2D plays a critical role in human MLL-r AML and uncover the MEF2D-CEBPE axis as a crucial transcriptional mechanism regulating leukemia cell self-renewal and differentiation block in MLL-r AML.
2021-10-02 | GSE165980 | GEO
Project description:Global expression profiles in Huh7 after infection with Lv-shMEF2D and Lv-scrambled, as well as transfection with siRNA-MEF2D and siRNA-control, were compared to investigate the molecular mechanisms involved in MEF2D-mediated regulation of cell cycle. In order to investigate the molecular mechanisms involved in MEF2D-mediated regulation of cell cycle, we assessed gene expression profiles in Huh7 cells after infection with Lv-shMEF2D and Lv-scrambled, as well as transfection with siRNA-MEF2D and siRNA-control, by cDNA microarray. Analysis of global mRNA expression profile indicated a shift toward G2/M arrest in the cells after downregulating MEF2D expression. The genes that inhibit G2/M transition were found to be expressed in high level in MEF2D-downregulated group, as compared with control group. Meanwhile, mRNA abundance of G2/M transition-promoting genes, except CDC2 and CDC25C, was reduced when MEF2D expression was depressed in Huh7 cells
2015-04-07 | E-GEOD-37123 | biostudies-arrayexpress