Next meeting : Thursday November 29th 2012, 10:00am – iRTSV

Fall is back and our next meeting is approaching ! Please note that the date changed, and the meeting will be on Thursday November 29th 2012, at 10:00 am at the iRSTV.

The location is the Maison Minatec (see below for more details, access map here).

Epigenetics NovemberThe speakers are :
Seminar by A. Arneodo (ENS Lyon)
Master replication origins at the heart of the organization and fragility of the human genome

Short talk by Edwige Hiriart (Verdel Lab, IAB)
RNA directed gene silencing in fission yeast

Short talk by Matthieu Benoit (Plevin Lab, IBS)
Insights into the recognition of an oncogenic microRNA precursor by the key cofactor TRBP during human microRNA biogenesis

Coffee break and lunch will be provided by Active Motif.

Please help us advertise the event! The full resolution flyer is accessible here.

Location : Maison Minatec, CEA Grenoble
This conference room is on the CEA campus, and the entrance is free !!

Located in front of the tram stop “Cité Internationale”, it is particularly easy to reach using public transportations (tramway, bus or train). It also has two parking lots nearby.

Click here to have a full size map.

Detailed program
10:00 Seminar by Dr. A. Arneodo (ENS Lyon)
Master replication origins at the heart of the organization and fragility of the human genome

In higher eukaryotes, the absence of specific sequence motifs marking the origins of replication has been a serious hindrance to the understanding of the mechanisms that regulate the initiation and the maintenance of the replication program in different cell types. During the course of evolution, mutations do not affect equally both strands of genomic DNA. In mammals, transcription-coupled nucleotide compositionalskews have been detected but no compositional asymmetry has been associated with replication.
In a first part, using a wavelet-based multi-scale analysis of human genome skew profiles, we identify a set of one thousand putative replication initiation zones. We report on recent DNA replication timing data that provide experimental verification of our in silico replication origin predictions.
In a second part, we examine the organisation of the human genes around the replication origins. We show that replication origins, gene orientation and gene expression are not randomly distributed but on the opposite are at the heart of a strong organisation of human chromosomes. The analysis of open chromatin markers brings evidence of the existence of accessible open chromatin around the majority of the putative replication origins that replicate early in the S phase.
We conclude by discussing the possibility that these “master’ replication origins also play a key role in genome dynamics during evolution and in pathological situations like cancer.

11:00 Short talk by Edwige Hiriart (Verdel Lab, IAB)
RNA directed gene silencing in fission yeast

11:30 Short talk by Matthieu Benoit (Plevin Lab, IBS)
Insights into the recognition of an oncogenic microRNA precursor by the key cofactor TRBP during human microRNA biogenesis

Micro-RNAs (miRNA) are small non-coding RNAs that regulate gene expression through RNA interference (RNAi). Human miRNAs are generated via a series of enzymatic processing steps. The precursor miRNA (pre-miRNA) is recognized and cleaved by a complex containing the RNase III enzyme, Dicer, and several non-catalytic accessory proteins. HIV TAR element binding protein (TRBP) is a constituent of the Dicer complex which augments complex stability and potentially functions in substrate recognition and product transfer to the RNA-induced silencing complex (RISC).
Here we have analyzed the interaction between the RNA-binding region of TRBP and the oncogenic human miRNA, miR-155, at different points in the miRNA biogenesis pathway. We show that the region of TRBP that binds miRNA precursors comprises two independent double-stranded RNA binding domains (dsRBDs) connected by a 60 residues flexible linker. No evidence of contact between the two dsRBDs was observed either in the apo form or in the RNA-bound state. The RNA-binding region of TRBP interacts non-cooperatively with pre-miR-155 and the related Dicer product miR-155/miR-155* and can form a complex with two protein molecules per RNA. Finally, we determined that the RNA-binding region of TRBP interacts with pre-miR-155 and miR-155/miR-155* via the same binding surface and with similar affinity, suggesting that the RNA binding region of TRBP could function before and after processing of pre-miRNAs by Dicer.

12:00 Lunch provided by Active Motif.