Genes are individualists, not collectivists, during early fruit fly development
Findings contradict previous scientific models that genes form hubs,
share resources

Date:
October 5, 2021
Source:
New York University
Summary:
Active genes do not form clusters and share resources during early
development in the fruit fly, according to a new study.



FULL STORY ========================================================================== Active genes do not form clusters and share resources during early
development in the fruit fly, according to a new study by New York
University and Princeton researchers published in the journal Current
Biology.


==========================================================================
"The study changes the way we think about how the molecular machinery
functions in basic cellular mechanisms during the development of
organisms," said Christine Rushlow, NYU professor of biology and the
study's senior author.

The nucleus is the portion of the cell containing the vast majority of
genetic information -- including the complex jumble of long cables of
DNA that make up the genome -- in order to determine the behavior of that organism. Genes stored in the sequence of DNA encode not just the protein sequence required to express the trait associated with that gene, but also
the information for when that protein sequence should be manufactured.

"The nucleus is an elaborate switchboard -- the connection point for
the vast array of information about the state of the cell's environment,
which will be processed and responded to by a defined set of expressed
protein products.

Within this framework, our study asked if there exists cooperation
between these hundreds of logic gates making individual decisions about
when to manufacture their respective proteins," said Peter Whitney, a
PhD student in NYU's Department of Biology and one of the study's authors.

Within the environment of the nucleus, it would make sense that genes
regulated by the same type of information would be concentrated in close proximity so that they might share resources, potentially lowering
the energetic cost of regulation. Several previous experiments have
shown a level of organization in the nucleus where genes occupy discrete domains. However, many of these studies use biochemical methods to define domains, rather than actually observing the physical position of the
active genes within the nucleus.

In the Current Biology study, the researchers demonstrated that they
could accurately identify the physical position of the active genes
using a microscopy imaging procedure and fruit flies, a model organism
commonly used in genetic and molecular research. The researchers examined
how a fertilized fruit fly egg develops into a fully formed organism,
a process that requires the activity of sets of genes, which become progressively activated during embryonic development.

Focusing on the earliest set of genes appearing in 90-minute-old fruit fly embryos, the researchers observed how a protein called Zelda regulates
the genes' transcription by recruiting the enzyme RNA Polymerase II
(Pol-II). Using high resolution microscopy and antibody staining, they visualized Pol-II at sites of nascent transcription on chromosomes.

By observing the positions of many genes using this method, they asked
the question: Are genes found in clusters? The answer was no.

"We hypothesized that genes might share pools of Pol-II in regulatory
hubs when they come into close proximity," said Rushlow. "However, our
data indicate that this is not the case, and genes in close proximity
each have their own Pol-II pool. This was surprising, as it goes against conventional wisdom and appears to directly contradict results from other methods." The researchers performed a series of follow-up experiments
to test the notion of functional clustering, such as looking for gene expression changes when genes were found in close proximity, or signs
of resources being shared among the genes visualized. Once again, they
did not find evidence of clustering.

In contrast to the idea that genes are spatially clustered and share transcriptional resources -- what one might call a "collectivist" model
-- the authors conclude that the data support an "individualist" model
of gene control at early genome activation in fruit flies.

========================================================================== Story Source: Materials provided by New_York_University. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Shao-Kuei Huang, Peter H. Whitney, Sayantan Dutta, Stanislav Y.

Shvartsman, Christine A. Rushlow. Spatial organization
of transcribing loci during early genome activation in
Drosophila. Current Biology, 2021; DOI: 10.1016/j.cub.2021.09.027 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211005124711.htm

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