Draft:Zelda

= Zelda (protein) =

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
In Drosophila, the zelda gene is on the X-chromosome.

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.

It colocalizes with chromatin and is expressed in structures, including the embryonic and larval nervous system, the extended germ band embryo, and ovaries.

Protein Structure
The dominant isoform of the Zelda protein has 1596 amino acids.

The protein mostly consists of intrinsically disordered regions but has six C2H2 zinc finger motifs. 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.

History
Zelda was discovered in 2006 by the Gerd Vorbrüggen lab at the Max Planck Institute for Chemical Biophysics and named Vielfältig, meaning diverse. Christine Rushlow's lab at New York University discovered that Zelda is an important regulator of early genome activator in 2008.

Function
Zelda binds to thousands of cis-regulatory modules and is necessary for transcriptional activation of the zygotic genome. Embryos without Zelda die.

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.

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.

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. 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.

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:
In eggs, Zelda transcripts are ubiquitously and uniformly distributed by the mother. In preblastoderm embryos, maternal transcripts and Zelda protein are also ubiquitously distributed.

Zelda is expressed by the zygote in mitotically active tissues such as the central nervous system, and the brain.

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:
Regulation of Zelda (look at paper about CLAMP)

Grainyhead and how it competes with Zelda, cGAP

cGAP

Homology:
Similar 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