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le jeudi 14 octobre à 11:00

Guillaume Filion (postdoc, The Netherlands Cancer Institute, Amsterdam)

Salle de formation du PRABI

par Vincent Daubin - 14 octobre 2010

Systematic protein-genome interaction maps reveal 5 chromatin types in Drosophila.

The local protein composition of chromatin controls important processes
such as transcription, replication and DNA repair, yet the diversity of
chromatin and its distribution along chromosomes is still poorly
characterized.

Using DamID in Drosophila Kc cells, we generated high-resolution
genome-wide binding maps of 53 chromatin proteins from a wide range of
functional categories. For most of those proteins, no binding data was
previously available.

By constructing a non supervised classifier, we find that there are five
principal chromatin
types defined by unique yet overlapping combinations of proteins.

Two types correspond to Polycomb and HP1-bound regions, respectively.
The novel ‘BLACK’ chromatin type covers half of the genome and induces
strong transcriptional repression on inserted transgenes. Remarkably,
this chromatin type is devoid of the classic ‘heterochromatin’ proteins
Polycomb and HP1. Thus, our data reveal the existence of a prominent
repressive chromatin type that has largely been overlooked.

Active genes are associated with one of the other two remaining
combinations of proteins. H3K36 methylation is associated with only one
of them, yet it was previously thought to mark every transcribed gene.
In addition, active genes involved in growth and cell proliferation, and
those involved in signal transduction are located in a distinct
chromatin types.

The five chromatin types modulate the interactions of transcription
factors with DNA. We observe that most transcription factors bind their
cognate motif only if it sits in the favored chromatin context. Our data
rule out a simple exclusion mechanism but support a model whereby
synergistic interactions target transcription factors to their binding site.

Finally, genomic regions in the 5 chromatin types follow different
evolutionary processes. The vast majority of synteny breaks with
Drosophila pseudoobscura occurs in only one of the transcriptionally
active types. Besides, the speed of evolution of genes located in that
chromatin type is higher than for other types.

In summary, our integrative approach identifies five major chromatin
types, which are defined by unique combinations of proteins and have
distinct functional properties.