Régulation des gènes

(Département Dynamique du Génome)

 

Responsable : Rosemary KIERNAN

 

All organisms must regulate the expression of their genes to achieve the silencing of certain genes, and the activation of others during development and homeostasis. Disregulation of gene expression frequently has dire consequences, and can lead to pathologies such as cancer. The regulation of gene expression occurs at different levels, all of which depend on a multitude of factors. Chromatin is a primary regulator of gene expression. Physical compaction of the genome into chromatin controls accessability to the transcription machinery. Studies performed over recent years have revealed the enormous complexity involved in modifying chromatin to regulate gene expression. Once the genome becomes accessible, engagement of the transcription machinery is a highly orchestrated process involving the recruitment of hundreds of factors that co-operate to achieve the expression of the gene. Finally, transcription of a gene is linked to cellular processes required for the maturation and export of the mRNA in order to achieve gene expression.

The Gene Regulation Laboratory is interested in understanding the mechanisms that contribute to the silencing or activation of mammalian genes. We use the promoter of the human immunodeficiency virus (HIV-1) as a model to study gene regulation in mammalian cells. Using this model, we have shown that the ubiquitin-proteasome system (UPS) strongly regulates HIV-1 transcription through recruitment of the 19S subunit to HIV-1 chromatin. We identified that a proteasome-associated protein, PAAF1, is a potent co-activator of transcription from the HIV-1 promoter. Ongoing studies are aimed at further characterizing the role of 19S and PAAF1 in transcription from HIV-1 and cellular promoters.

We have also shown that the HIV-1 promoter is repressed by HP1γ-dependent heterochromatin formation. We are further characterizing the repressive mechanisms that downregulate HIV-1 transcription, and to determine whether similar mechanisms operate at cellular promoters.

 

Mots clé : transcription, chromatine, ubiquitine, protéasome

 

Actualités de l'équipe

Postdoctoral position in gene regulation Applications are currently being accepted for a postdoctoral position in the Gene Regulation laboratory at the Institute of Human Genetics, Montpellier, France. The Gene Regulation lab is interested in understanding the mechanisms that contribute to the silencing or activation of mammalian genes. We use the promoter of the human immunodeficiency virus (HIV-1) as a model to study gene regulation in mammalian cells. Qualifications: Candidates should hold a PhD degree or equivalent and have a strong background in molecular biology, particularly chromatin biology, and cell biology. Applicants should send their resume and the name and contact details of two references to Rosemary Kiernan (Rosemary.Kiernan@igh.cnrs.fr).

 

Les 2 dernières publications de l'équipe :

Nakamura M, Basavarajaiah P, Rousset E, Beraud C, Latreille D, Henaoui IS, Lassot I, Mari B, Kiernan R.. Spt6 levels are modulated by PAAF1 and proteasome to regulate the HIV-1 LTR (2012), Retrovirology : 9(1):13

[Medline - Abstract]

Wagschal, A., Rousset, E., Basavarajaiah, P., Contreras, X. , Harwig, A., Laurent-Chabalier, S. , Nakamura, M., Chen, X., Zhang, K., Meziane, O., Boyer, F., Parrinello, H., Berkhout, B., Terzian, C., Benkirane, M., Kiernan, R. . Microprocessor, Setx, Xrn2 and Rrp6 Co-Operate to Induce Premature Termination of Transcription by RNAPII (2012), CELL : 150, 1147-1157, http://dx.doi.org/10.1016/J.cell.2012.08.004

[Medline - Abstract]

 

Toutes les publications de l'équipe

Personnel de l'équipe :

Nom / prénom	Localisation	Poste	Situation
Chercheur
CONTRERAS Xavier	S23	9974	CR (INSERM)
KIERNAN Rosemary	S23	9974	CR (CNRS) + HDR
Post-Doc
BARBIER Jérôme	S23	9974	(CNRS)
BASAVARAJAIAH Poornima	S23	9974	(CNRS)
CDD
BLUY Lisa	S23	9974	AI (CNRS)
LATREILLE Daniel	S16	9988	IR (CNRS)