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Spatiotemporal control of gene expression

Understanding how transcriptional programmes drive developmental processes and maintain cellular identity represents a major challenge. To decipher the transcriptional network during cell differentiation, it is important to comprehend the interactions between genomic regulatory elements.
Spatiotemporal control of gene expression
Cells of the blood and immune system originate from a common ancestor, the haematopoietic stem cell (HSC), which resides in the bone marrow. HSC differentiation into mature blood cells depends on cell type and developmental stage specific gene expression. This is achieved through the integrated action of transcription factors that bind to promoters, enhancers as well as other regulatory elements in the genome.

Promoters lie adjacent to genes while enhancers are located in a much more sporadic manner and often far away from target genes. Accumulating evidence indicates that the contact between distal enhancers and promoters is mediated by chromatin looping, bringing these regions into close vicinity and facilitating the binding of transcription factors.

The EU-funded GENOMIC INTERACTIONS (B-cell development and gene regulation in three dimensions) project wished to map promoter-enhancers interactions throughout haematopoietic development. Towards this goal, scientists performed genomic analysis of HSCs as well as later progeny, using chromatin immunoprecipitation sequencing and RNA sequencing platforms.

The generated data led to the establishment of enhancer maps of B-cell as well as myeloid cell development alongside maps of open chromatin and RNA expression profiles. Results showed clear pre-establishment of B-cell related enhancers in early progenitor cells, which however, remained functionally inactive. Additional work in transcription factor knockout mouse models is required to fully elucidate the contribution of these enhancers in early lymphoid development. Furthermore, the consortium established a protocol for mapping interactions between promoters and enhancers on a genome-wide level using few cells.

Overall, the findings of the study bring us a step closer to understanding how transcriptional networks drive developmental progression within the frame of B-cell differentiation, especially in the context of long-range genomic interactions that mediate promoter-enhancer contact. Also, the results suggest potential functional consequences of genetic variants in regions associated with complex genetic traits or hereditary diseases.

Related information

Subjects

Life Sciences

Keywords

Regulatory element, transcription factor, chromatin looping, GENOMIC INTERACTIONS, B cell
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