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SUMMARY:Beyond chromatin: Histones as developmental regulators in Drosophi
 la - Professor Amanda Amodeo from Dartmouth College\, Hanover\, USA  
DTSTART:20240123T130000Z
DTEND:20240123T140000Z
UID:TALK202213@talks.cam.ac.uk
CONTACT:Caroline Newnham
DESCRIPTION:The newly fertilized embryo is an unusually large and undiffer
 entiated cell. In many species\, including Drosophila melanogaster\, the f
 irst hours of development are spent partitioning that large cell into thou
 sands of smaller cells before zygotic genome activation (ZGA) and cell cyc
 le slowing at a developmental transition known as the Mid-Blastula Transit
 ion (MBT). The timing of the MBT is controlled by the increasing Nuclear t
 o Cytoplasmic (N/C) ratio as the embryo divides without growth. We have so
 ught to characterize the molecular mechanisms which allow for N/C ratio se
 nsing in the early embryo. We have found that a large pool of maternally p
 rovided histone protein is consumed by the burgeoning amount of zygotic DN
 A. We show that this leads to de-repression of the cell cycle inhibitor Ch
 k1\, which directly interacts with the N-terminal tail of histone H3. This
  provides a direct link between the N/C ratio and cell cycle slowing at th
 e MBT and a surprising novel role for histones as cell cycle regulators. A
 t the same time\, as the maternal supply of H3 is exhausted the amount of 
 its variant\, H3.3 increases on the zygotic chromatin. In other tissues H3
 .3 is known to associate with active promoters and enhancers as well as he
 terochromatin domains\, suggesting a link between H3.3 incorporation and c
 hromatin changes that have long been observed during ZGA. These changes in
  nuclear H3 and H3.3 nuclear import and incorporation are sensitive to the
  local N/C ratio. Thus\, changes in the nuclear availability of H3 may con
 tribute to cell cycle slowing and transcriptional activation through multi
 ple mechanisms during the MBT. Ongoing work seeks to understand the affect
 s of histone H3 outside of chromatin in later stages of development and to
  measure more global changes in nuclear composition leading up to the MBT.
  
LOCATION:Biffen Lecture theatre and Zoom
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