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Zelda (protein)
edit| Zelda | |
|---|---|
| Identifiers | |
| Symbol | Zld, Vlg |
| Alt. names | Vielfaltig |
Zelda (Zld), (Zinc-finger early Drosophila activator) also known as Vielfältig (Vfl), is a master transcription factor and pioneer factor that activates the transcription of a wide range of genes in the early Drosophila embryo.
Gene
editIn Drosophila, the zelda gene is on the X-chromosome. [1]
The zelda gene has been shown to enable chromatin loop anchoring activity, nucleosome binding activity, and transcription cis-regulatory region binding activity. It is also involved in processes, including positive regulation of gastrulation, positive regulation of macromolecule metabolic process, and positive regulation of neuroblast proliferation. [1]
It colocalizes with chromatin and is expressed in structures, including the embryonic and larval nervous system, the extended germ band embryo, and ovaries. [1]
Protein Structure
editThe dominant isoform of the Zelda protein has 1596 amino acids. [2]
The protein mostly consists of intrinsically disordered regions but has six C2H2 zinc finger motifs [3]. Four of those are clustered at the C-terminal end of the protein and make up Zelda's DNA binding domain, while the other two are located near the N-terminus. [2]
History
editZelda was discovered in 2006 by the Gerd Vorbrüggen lab at the Max Planck Institute for Chemical Biophysics and named Vielfältig, meaning diverse. [3] Christine Rushlow's lab at New York University discovered that Zelda is an important regulator of early genome activator in 2008. [4]
Function
editZelda binds to thousands of cis-regulatory modules [2] and is necessary for transcriptional activation of the zygotic genome. [5] Embryos without Zelda die. [5]
ZLD drives expression of a small number of genes as early as the eighth mitotic division and is required for the later activation of hundreds of genes during the major wave of zygotic genome activation at mitotic cycle 14. [6]
Genes that require Zelda for expression are components of the RNA degradation pathways that destabilize maternal RNAs, including zygotically expressed miRNAs and lncRNAs. Zelda supplied to the zygote by the mother is essential for zygotic genome activation and maternal mRNA decay and drives the coordinated transition from maternal to zygotic control. Zelda supplied by the zygote is also required for development. [2]
Zelda's intrinsically disordered/low-complexity domains are thought to facilitate protein-protein interactions that mediate the formation of higher order structures, including phase separated domains or "hubs" of high local concentrations. [7] [8] [9] Though there is a growing body of research linking these structures to transcriptional regulation, much is unclear about their role. One hypothesis is that domains formed by homo- and heterotypic interactions between intrinsically disordered regions serve to locally enrich transcription factors, potentially in the vicinity of their targets, thereby altering their local concentration and modulating their binding dynamics.[10]
Go into specifics of how Zelda activates genes (pioneer factor)
It has been shown that Zelda increases chromatin accessibility.
Target genes
Mechanism by which it does so: phase separation, hubs, etc
CAGGTAG motif
Does stuff in larvae -> imaginal disks
Distribution over time:
editIn eggs, Zelda transcripts are ubiquitously and uniformly distributed by the mother. In preblastoderm embryos, maternal transcripts and Zelda protein are also ubiquitously distributed. [3]
Zelda is expressed by the zygote in mitotically active tissues such as the central nervous system, and the brain. [11]
Zelda is a nuclear protein. During the rapid nuclear cycles in the early embryo, it associates with chromatin during interphase. During mitosis, it dissociates from chromatin to exist in the nucleoplasm.
How it is left over from maternal RNA
As embryogenesis progresses, Zelda concentration decreases.
Increases in larvae
Regulation:
editRegulation of Zelda (look at paper about CLAMP)
Grainyhead and how it competes with Zelda, cGAP
cGAP
Homology:
editSimilar in cockroaches other insects (look at honey bees, etc)
Homologs in humans? (its a bunch of different TFs)
Homolog, paralog, ortholog
Mention somewhere what happens in the absence of Zelda at different points in time
https://www.thenakedscientists.com/articles/science-features/gene-month-zelda
https://twitter.com/mpi_ie/status/1468523599040552964
https://www.cell.com/current-biology/pdfExtended/S0960-9822(19)30317-3
https://www.michaeleisen.org/blog/?p=617
See Also
edit
External Links
edithttps://www.thenakedscientists.com/articles/science-features/gene-month-zelda
https://twitter.com/mpi_ie/status/1468523599040552964
https://www.cell.com/current-biology/pdfExtended/S0960-9822(19)30317-3
https://www.michaeleisen.org/blog/?p=617
References
edit- ^ a b c "zld zelda [Drosophila melanogaster (fruit fly)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2022-12-27.
- ^ a b c d Hamm, Danielle C.; Larson, Elizabeth D.; Nevil, Markus; Marshall, Kelsey E.; Bondra, Eliana R.; Harrison, Melissa M. (2017-12-19). "A conserved maternal-specific repressive domain in Zelda revealed by Cas9-mediated mutagenesis in Drosophila melanogaster". PLOS Genetics. 13 (12): e1007120. doi:10.1371/journal.pgen.1007120. ISSN 1553-7404. PMC 5752043. PMID 29261646.
This article incorporates text from this source, which is available under the CC BY 4.0 license.
- ^ a b c Staudt, Nicole; Fellert, Sonja; Chung, Ho-Ryun; Jäckle, Herbert; Vorbrüggen, Gerd (May 2006). "Mutations of theDrosophilaZinc Finger-encoding GenevielfältigImpair Mitotic Cell Divisions and Cause Improper Chromosome Segregation". Molecular Biology of the Cell. 17 (5): 2356–2365. doi:10.1091/mbc.e05-11-1056. ISSN 1059-1524. PMC 1446075. PMID 16525017.
- ^ Liang, Hsiao-Lan; Nien, Chung-Yi; Liu, Hsiao-Yun; Metzstein, Mark M.; Kirov, Nikolai; Rushlow, Christine (2008-11-20). "The zinc-finger protein Zelda is a key activator of the early zygotic genome in Drosophila". Nature. 456 (7220): 400–403. Bibcode:2008Natur.456..400L. doi:10.1038/nature07388. ISSN 1476-4687. PMC 2597674. PMID 18931655.
- ^ a b Liang, Hsiao-Lan; Nien, Chung-Yi; Liu, Hsiao-Yun; Metzstein, Mark M.; Kirov, Nikolai; Rushlow, Christine (2008-11-20). "The zinc-finger protein Zelda is a key activator of the early zygotic genome in Drosophila". Nature. 456 (7220): 400–403. Bibcode:2008Natur.456..400L. doi:10.1038/nature07388. ISSN 1476-4687. PMC 2597674. PMID 18931655.
- ^ Harrison, Melissa M.; Li, Xiao-Yong; Kaplan, Tommy; Botchan, Michael R.; Eisen, Michael B. (2011-10-20). "Zelda Binding in the Early Drosophila melanogaster Embryo Marks Regions Subsequently Activated at the Maternal-to-Zygotic Transition". PLOS Genetics. 7 (10): e1002266. doi:10.1371/journal.pgen.1002266. ISSN 1553-7404. PMC 3197655. PMID 22028662.
- ^ Kato, Masato; McKnight, Steven L. (2018-06-20). "A Solid-State Conceptualization of Information Transfer from Gene to Message to Protein". Annual Review of Biochemistry. 87 (1): 351–390. doi:10.1146/annurev-biochem-061516-044700. ISSN 0066-4154. PMID 29195049. S2CID 28314614.
- ^ Brangwynne, Clifford P.; Eckmann, Christian R.; Courson, David S.; Rybarska, Agata; Hoege, Carsten; Gharakhani, Jöbin; Jülicher, Frank; Hyman, Anthony A. (2009-06-26). "Germline P Granules Are Liquid Droplets That Localize by Controlled Dissolution/Condensation". Science. 324 (5935): 1729–1732. Bibcode:2009Sci...324.1729B. doi:10.1126/science.1172046. ISSN 0036-8075. PMID 19460965. S2CID 42229928.
- ^ Mir, Mustafa; Stadler, Michael R; Ortiz, Stephan A; Hannon, Colleen E; Harrison, Melissa M; Darzacq, Xavier; Eisen, Michael B (2018-12-27). Singer, Robert H; Struhl, Kevin; Crocker, Justin (eds.). "Dynamic multifactor hubs interact transiently with sites of active transcription in Drosophila embryos". eLife. 7: e40497. doi:10.7554/eLife.40497. ISSN 2050-084X. PMC 6307861. PMID 30589412.
- ^ Tsai, Albert; Muthusamy, Anand K; Alves, Mariana RP; Lavis, Luke D; Singer, Robert H; Stern, David L; Crocker, Justin (2017-11-02). Arnosti, David N (ed.). "Nuclear microenvironments modulate transcription from low-affinity enhancers". eLife. 6: e28975. doi:10.7554/eLife.28975. ISSN 2050-084X. PMC 5695909. PMID 29095143.
- ^ Staudt, Nicole; Fellert, Sonja; Chung, Ho-Ryun; Jäckle, Herbert; Vorbrüggen, Gerd (May 2006). "Mutations of the Drosophila zinc finger-encoding gene vielfältig impair mitotic cell divisions and cause improper chromosome segregation". Molecular Biology of the Cell. 17 (5): 2356–2365. doi:10.1091/mbc.e05-11-1056. ISSN 1059-1524. PMC 1446075. PMID 16525017.
