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Chromatin and Transcription

RNA polymerase II (RNAPII) is 12-subunit enzyme responsible for the production of all protein-coding RNA. It also transcribes a number of small RNAs (snRNA and miRNAs) and a majority of long non coding RNAs (lncRNA). Transcription by RNA polymerase II involves several steps and a number of proteins:

Transcription by RNAPII

Transcription occurs in the context of chromatin, which is defined by the association of DNA with histone proteins. DNA (~147bp) is wrapped around the nucleosome, an octamer that consists of two copies of each of the four core histone proteins (H2A, H2B, H3 and H4). Further chromatin compaction involves histone H1 that binds between nucleosomes.

From DNA to chromatin 0321_DNA_Macrostructure.jpg” By OpenStax CC BY 4.0, via Wikimedia Commons

Transcription factors, architectural proteins (e.g. insulators) and RNAPII thus interact with a number of proteins that are able to modify histones (e.g. HAT or histone acetyltransferases) and to move nucleosomes (e.g. ATP-dependent chromatin remodeling complexes).

I started to become more interested in transcription and chromatin organization in 2013-2015, when I joined the group of Olivier Cuvier at the CBI / LBME (CNRS / Univ. Toulouse), in order to develop my skills in genomics and bioinformatics.

During these 2 years, I participated in 2 published studies:

  • A study on Drosophila insulator binding proteins (IBPs) in which we found that ChIP-seq peaks representing indirect protein-DNA interactions could be used to decipher the long-range targets of IBPs and their interaction with promoter-proximal pausing of RNAPII (Liang et al., Mol Cell, 2014)

  • A study in collaboration with the group of Monsef Benkirane showing that subunits of the Integrator complex interact with NELF and play a role genome-wide in NELF-mediated RNAPII pause/release (Stadelmayer et al., Nat Commun, 2014).

During this period I also collaborated closely with the group of Jérôme Cavaillé to uncover the molecular mechanisms underlying the neonatal mortality in a murine model deficient for a cluster of miRNA (Labialle et al., EMBO J, 2014).

In 2015-2018, I obtained an Agreenskills+ fellowship and joined the group of Scott Michaels. I worked in close collaboration with Xuhong Yu to unravel the function of a new family of negative transcription elongation factors on RNAPII transcription and chromatin looping. The analysis of our NGS (Next-generation Sequencing) data allowed me to propose a mechanism by which these proteins modulate gene expression and to uncover the role of the genomic neighborhood in these effects. I am now finalizing the GeneNeighborhood R package to allow others to explore the orientation and proximity of the direct upstream and downstream neighbors of their genes of interest.

Publications

(2015). Integrator complex regulates NELF-mediated RNA polymerase II pause/release and processivity at coding genes.. Nat Commun. 2014 Nov 20;5:5531..

Project PubMed

(2015). The miR-379/miR-410 cluster at the imprinted Dlk1-Dio3 domain controls neonatal metabolic adaptation.. EMBO J. 2014 Oct 1;33(19):2216-30..

Project PubMed

(2014). Chromatin immunoprecipitation indirect peaks highlight long-range interactions of insulator proteins and Pol II pausing.. Mol Cell. 2014 Feb 20;53(4):672-81..

Project PubMed

(2011). Transcriptomic and nuclear architecture of immune cells after LPS activation.. Chromosoma. 2011 Oct;120(5):501-20..

Project PubMed

Talks