Cell-type-specific chromatin occupancy by the pioneer factor Zelda drives key developmental transitions in Drosophila
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ABSTRACT:
PROVIDER: PRJNA634111 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11818933.fastq.gz | Fastqsanger.gz | |||
| SRR11818934.fastq.gz | Fastqsanger.gz | |||
| SRR11818935.fastq.gz | Fastqsanger.gz | |||
| SRR11818936.fastq.gz | Fastqsanger.gz | |||
| SRR11818937.fastq.gz | Fastqsanger.gz |
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Project description:During early Drosophila embryogenesis, the essential pioneer factor Zelda defines hundreds of cis-regulatory regions and in doing so reprograms the zygotic transcriptome. While Zelda is essential later in development, it is unclear how the ability of Zelda to define cis-regulatory regions is shaped by cell-type specific chromatin architecture established during differentiation. Asymmetric division of neural stem cells (neuroblasts) in the fly brain provide an excellent paradigm for investigating the cell-type specific functions of this pioneer factor. Zelda is expressed in neuroblasts, and we show that Zelda synergistically functions with Notch to maintain neuroblasts in an undifferentiated state. Zelda misexpression can reprogram progenitor cells to neuroblasts, but this capacity is limited by transcriptional repressors critical for progenitor commitment. Zelda genomic occupancy in neuroblasts is reorganized as compared to the embryo, despite sharing many target genes in these two developmental stages. This reorganization is likely driven by differences in chromatin accessibility and cofactor availability. We propose that Zelda regulates essential transitions in the neuroblasts and embryo through a shared gene regulatory network by defining cell-type specific enhancers.
2021-11-05 | GSE150931 | GEO
Project description:During Drosophila embryogenesis, the essential pioneer factor Zelda defines hundreds of cis-regulatory regions and in doing so reprograms the zygotic transcriptome. While Zelda is essential later in development, it is unclear how the ability of Zelda to define cis-regulatory regions is shaped by cell-type-specific chromatin architecture. Asymmetric division of neural stem cells (neuroblasts) in the fly brain provide an excellent paradigm for investigating the cell-type-specific functions of this pioneer factor. We show that Zelda synergistically functions with Notch to maintain neuroblasts in an undifferentiated state. Zelda misexpression reprograms progenitor cells to neuroblasts, but this capacity is limited by transcriptional repressors critical for progenitor commitment. Zelda genomic occupancy in neuroblasts is reorganized as compared to the embryo, and this reorganization is correlated with differences in chromatin accessibility and cofactor availability. We propose that Zelda regulates essential transitions in the neuroblasts and embryo through a shared gene-regulatory network driven by cell-type-specific enhancers.
| S-EPMC8660810 | biostudies-literature
Project description:Pioneer factors such as Zelda initiate zygotic transcription within Drosophila early embryos, but whether other factors also support this dynamic patterning process is unclear. Odd-paired (Opa) is a zinc-finger transcription factor expressed during cellularization, shown to act as timing factor to control pair-rule to segmental patterning transition along the anterior-posterior (AP) axis. We found Opa regulates expression through an enhancer active along the dorso-ventral axis (sog_Distal), specifically, to support its late embryonic expression. Opa chromatin immunoprecipitation identified occupancy at this enhancer sequence as well widespread binding throughout the genome, comparable to Zelda. Furthermore, chromatin assays (ATAC-seq) demonstrate that Opa, like Zelda, influences accessibility and has both common as well as distinct target sequences. opa mutants also exhibit DV and AP patterning changes suggesting Opa acts broadly. This study suggests Opa is a late-acting, pioneer factor whose action follows Zelda to herald in a second wave of zygotic gene expression. NIH Grants R35GM118146 and R03HD097535 to A.S.
2020-08-02 | GSE140722 | GEO
Project description:For a damaged tissue to regenerate, the injured site must repair the wound, proliferate, and restore the correct patterning and cell types. We found that Zelda, a pioneer transcription factor largely known for its role in embryonic zygotic genome activation, is dispensable for normal wing development but crucial for wing disc patterning during regeneration. Impairing Zelda function during disc regeneration resulted in adult wings with a plethora of cell fate errors, affecting the veins, margins, and posterior compartment identity. Using CUT&RUN, we identified and validated targets of Zelda including the cell fate genes cut, Delta and achaete, which failed to return to their normal expression patterns upon loss of Zelda. In addition, Zelda controls expression of factors previously established to preserve cell fate during regeneration like taranis and osa, which stabilizes engrailed expression during regeneration, thereby preserving posterior identity. Finally, Zelda ensures proper expression of the integrins encoded by multiple edematous wings and myospheroid during regeneration to prevent blisters in the resulting adult wing. Thus, Zelda is crucial for maintaining cell fate and structural architecture of the regenerating tissue.
2024-06-26 | GSE268674 | GEO
Project description:The pioneer transcription factor Zelda (ZLD) increases the accessibility of chromatin to promote the essential process of zygotic genome activation (ZGA) in the Drosophila early embryo. However, many genomic loci remain accessible in the absence of ZLD and are enriched for GA-rich DNA binding motifs. Therefore, we hypothesized that other pioneer TFs that function with ZLD have not yet been identified, especially those that bind to GA-rich motifs. CLAMP (Chromatin-linked adaptor for Male-specific lethal MSL proteins) is a GA-rich motif binding TF that is essential for early embryonic development. Here, we identify for the first time that CLAMP is a pioneer TF which interacts directly with nucleosomes, regulates zygotic genome activation, promotes chromatin accessibility, and facilitates the binding of ZLD to promoters. When ZLD is bound at a locus but does not regulate chromatin accessibility, CLAMP can often function redundantly to open the chromatin. Because ZGA is an essential process across metazoans, it is key to evolve redundant pioneer TFs to protect organisms from lethality that would be caused by loss of a single non-redundant factor.
2021-08-05 | GSE152598 | GEO
Project description:The pioneer transcription factor Zelda (ZLD) increases the accessibility of chromatin to promote the essential process of zygotic genome activation (ZGA) in the Drosophila early embryo. However, many genomic loci remain accessible in the absence of ZLD and are enriched for GA-rich DNA binding motifs. Therefore, we hypothesized that other pioneer TFs that function with ZLD have not yet been identified, especially those that bind to GA-rich motifs. CLAMP (Chromatin-linked adaptor for Male-specific lethal MSL proteins) is a GA-rich motif binding TF that is essential for early embryonic development. Here, we identify for the first time that CLAMP is a pioneer TF which interacts directly with nucleosomes, regulates zygotic genome activation, promotes chromatin accessibility, and facilitates the binding of ZLD to promoters. When ZLD is bound at a locus but does not regulate chromatin accessibility, CLAMP can often function redundantly to open the chromatin. Because ZGA is an essential process across metazoans, it is key to evolve redundant pioneer TFs to protect organisms from lethality that would be caused by loss of a single non-redundant factor.
2021-08-05 | GSE152596 | GEO
Project description:While chromatin presents a barrier to the binding of many transcription factors, pioneer factors access nucleosomal targets and promote chromatin opening. Despite binding to target motifs in closed chromatin, many pioneer factors display cell-type specific binding and activity. The mechanisms governing pioneer-factor occupancy and the relationship between chromatin occupancy and opening remain unclear. We studied three Drosophila transcription factors with distinct DNA-binding domains and biological functions: Zelda, Grainy head, and Twist. We demonstrated that the level of chromatin occupancy is a key determinant of activity. Multiple factors regulate occupancy, including motif content, local chromatin, and protein concentration. Regions outside the DNA-binding domain are required for binding and chromatin opening. Our results show that pioneering activity is not a binary feature intrinsic to a protein but occurs on a spectrum and is regulated by a variety of protein-intrinsic and cell-type-specific features.
2023-05-02 | GSE227883 | GEO
Project description:While chromatin presents a barrier to the binding of many transcription factors, pioneer factors access nucleosomal targets and promote chromatin opening. Despite binding to target motifs in closed chromatin, many pioneer factors display cell-type specific binding and activity. The mechanisms governing pioneer-factor occupancy and the relationship between chromatin occupancy and opening remain unclear. We studied three Drosophila transcription factors with distinct DNA-binding domains and biological functions: Zelda, Grainy head, and Twist. We demonstrated that the level of chromatin occupancy is a key determinant of activity. Multiple factors regulate occupancy, including motif content, local chromatin, and protein concentration. Regions outside the DNA-binding domain are required for binding and chromatin opening. Our results show that pioneering activity is not a binary feature intrinsic to a protein but occurs on a spectrum and is regulated by a variety of protein-intrinsic and cell-type-specific features.
2023-05-02 | GSE227882 | GEO
Project description:While chromatin presents a barrier to the binding of many transcription factors, pioneer factors access nucleosomal targets and promote chromatin opening. Despite binding to target motifs in closed chromatin, many pioneer factors display cell-type specific binding and activity. The mechanisms governing pioneer-factor occupancy and the relationship between chromatin occupancy and opening remain unclear. We studied three Drosophila transcription factors with distinct DNA-binding domains and biological functions: Zelda, Grainy head, and Twist. We demonstrated that the level of chromatin occupancy is a key determinant of activity. Multiple factors regulate occupancy, including motif content, local chromatin, and protein concentration. Regions outside the DNA-binding domain are required for binding and chromatin opening. Our results show that pioneering activity is not a binary feature intrinsic to a protein but occurs on a spectrum and is regulated by a variety of protein-intrinsic and cell-type-specific features.
2023-05-02 | GSE227881 | GEO
Project description:While chromatin presents a barrier to the binding of many transcription factors, pioneer factors access nucleosomal targets and promote chromatin opening. Despite binding to target motifs in closed chromatin, many pioneer factors display cell-type specific binding and activity. The mechanisms governing pioneer-factor occupancy and the relationship between chromatin occupancy and opening remain unclear. We studied three Drosophila transcription factors with distinct DNA-binding domains and biological functions: Zelda, Grainy head, and Twist. We demonstrated that the level of chromatin occupancy is a key determinant of activity. Multiple factors regulate occupancy, including motif content, local chromatin, and protein concentration. Regions outside the DNA-binding domain are required for binding and chromatin opening. Our results show that pioneering activity is not a binary feature intrinsic to a protein but occurs on a spectrum and is regulated by a variety of protein-intrinsic and cell-type-specific features.
2023-05-02 | GSE227880 | GEO