Bioinformatics Seminars

Bioinformatics Seminar

Time: 10:45am Tuesdays.
Venue:
Level 7 Seminar Room 2, WEHI1

21 November 2017

Seminar Room 1

Emergence of chromatin architecture during early embryogenesis

Juanma Vaquerizas
Max Planck Institute

The three dimensional organisation of the genome plays a fundamental
role in the regulation of gene expression. Recent examinations of
chromatin conformation have revealed the presence of hundreds of
self-associating domains and thousands of regulatory loops between
enhancers and target genes that ensure a correct deployment of
developmental programmes. Mutations affecting these highly conserved
and relatively tissue-unspecific regulatory features often result in
striking developmental defects and disease. Despite the
characterisation of such regulatory features, it is currently unknown
when chromatin conformation is established and the cellular mechanisms
that drive this process.

Here, using Drosophila as a model system, we investigated chromatin
conformation in tightly staged, hand-sorted embryos at different time
points during early development. In situ Hi-C maps for these embryos
revealed that chromatin structure is significantly remodelled at
hundreds of loci during embryo development. We further demonstrate
that specific expressed loci serve as nucleation sites for early
topologically associating domain (TAD) boundaries. Strikingly,
inhibition of RNA polymerase II does not preclude the formation of
TADs, suggesting that transcription is not necessary for the
establishment of such domains. However, reduction of RNA polymerase II
activity results in a marked decrease of insulation between
topological domains. Our results have important implications for our
understanding of how the three-dimensional structure of the genome is
established and the mechanisms that trigger this organisation.


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