Sets of distal enhancer elements bound by the LDB1 transcription factor complex (orange ovals, numbers indicate distance in kb from MYB promoter) interact with the MYB gene promoter and first intron through chromatin loops. Transcription factor-bound regulatory elements cluster around MYB to form an active chromati hub (ACH), stimulating transcription (left).Under normal conditions, terminal erythroid differentiation is accompanied by strong decrease in LDB1 complex binding at distal enhancer sites, loss of looping and dramatic decrease in MYB expression (top right). Presence of intergenic non-coding variants (Single Nucleotide Polymorphisms, or SNPs) affect local transcription factor binding at distal enhancer sites (here at -84kb enhancer) and diminish looping frequency and MYB expression (bottom righ), explaining the effect of trait-associated intergenic SNPs on MYB regulation. Lower MYB levels subsequently affect red cell traits.
Model of MYB oncogene regulation in erythroid cells
Eric Soler and his research group are investigating mechanisms regulating spatio-temporal control of gene expression. They investigate the relationships existing between chromosome folding, genome architecture and gene expression during cellular differentiation and development. They use red blood cell differentiation as a model to conduct epigenomic studies of normal differentiation processes. They also investigate the genetic mechanisms of both frequent and rare red blood cells disorders such as beta-thalassemia and erythroid leukemias.
Our group (Laboratory of Molecular Hematopoiesis), investigates molecular mechanisms controlling gene expression, with strong emphasis on long-range genomic interactions, and associated pathological disorders in erythroid cells.
The major goal of the laboratory of molecular hematopoiesis is to understand how genes are controlled in time and space during dynamic processes such as cellular differentiation and development. We use hematopoiesis, and specifically eythropoiesis, as a biological system to dissect the molecular events leading to fine tuning of gene expression.
Gene expression over long genomic distances
We focus our attention on the LDB1 transcription factor complex, a major regulator of erythroid differentiation, allowing control of gene expression over long genomic distances (from several kb up to 1 Mb) through the establishment of chromatin loops connecting distal enhancers with their target genes. These types of long-range interactions are critical in gene regulatory networks and may be affected in several diseases. We showed for instance that long-range enhancer-gene interactions at the HBS1L-MYB locus are affected by genomic variants, resulting in modulation of disease severity in beta-thalassemia patients, underscoring the need to decipher such long-range interactions across the genome and to understand their impacts on gene expression.
We are focusing on different erythroid disorders such as beta thalassemias and sickle cell anemia, which are among the most common inherited genetic disorders in humans and acute erythroid leukemias, a rare but particularly aggressive subtype of leukemia for which therapeutic options are dramatically limited.
• 2016 : Habilitation à diriger des recherches (HDR), Université de Montpellier
• 2016 : Appointed Team Leader at the IGMM (Molecular Genetics Institute of Montpellier), France
• 2014 : Appointed Atip-Avenir Group leader at Inserm UMR967, CEA iRCM institute, Fontenay-aux-Roses, France
• 2013 : Appointed Research associate (Inserm CR1, permanent position), Inserm UMR967, Fontenay-aux-Roses, France
•2010-2012 : Appointed Group Leader at the Erasmus Medical Center, Rotterdam, The Netherlands
• 2006-2010 : Postdoctoral fellow, Erasmus Medical Center, Rotterdam, the Netherlands, Frank Grosveld's lab
• 2005 PhD, Université Paris 7, France, Louis-Marie Houdebine's lab
• Member of the Laboratory of Excellence (LabEx) EpiGenMed, Montpellier, 2016
• Member of the LabEx on Red Blood Cells GR-Ex, 2015
• Atip-Avenir Grant, (Inserm), 2013
Nov 2015, Nat Commun.
March 2015, Blood
April 2014, J Clin Invest