Speaker: Dr. Alvaro Rada-Iglesias
Stanford University, USA

Organizer: IRB Barcelona  & IBMB-CSIC
Host: Dr. Marco Milan, IRB Barcelona
Date: Friday, 20 January 2012, 12:00h
Place: Aula Fèlix Serratosa, Parc Cièntific de Barcelona, Spain

Abstract

During human embryonic development, remarkable cellular diversity is generated from a single set of genetic information (i.e. the genome); yet, each different cell type expresses a specific set of genes and displays unique molecular and functional properties. In this context, a group of distal regulatory elements, known as enhancers, plays a preponderant role in the establishment of cell-type and developmental-stage specific gene expression profiles. However, these regulatory elements are difficult to identify, since they lack strong defining features and show limited sequence conservation. As a result, we currently know of few mammalian and even less human developmental enhancers.
We have recently developed an epigenomic strategy that allows the identification of enhancers in a sequence conservation and cell-type independent manner. Combined with in vitro differentiation models based on human embryonic stem cells (hESC), we used this strategy to characterize the enhancer repertoire of pluripotent (i.e. hESC) and multipotent (i.e. human neural crest cells (hNCC)) human embryonic cell populations. In hESC, we have uncovered a unique chromatin signature that identifies a novel class of enhancers, which are inactive but poised in hESC and that become active upon differentiation, during the early stages of human embryogenesis and in a lineage-specific manner. Similarly, our epigenomic approach allowed us to characterize enhancers in human neural crest, a hitherto largely inaccessible and biochemically intractable vertebrate-specific embryonic cell population. The NCC display remarkable migratory and differentiation potential and contribute to the formation of multiple tissues and organs, such as the peripheral nervous system and most of the facial bones and cartilages. Using the sequence information contained within hNCC enhancers, we uncovered NR2F1 and NR2F2, two orphan nuclear receptors, as novel neural crest and craniofacial regulators. All in all, our studies have largely expanded the current catalog of human developmental enhancers, which has far reaching implications for the understanding of the genetic basis of human complex diseases and human morphological evolution.