Chromatin priming elements direct tissue-specific gene activity before hematopoietic specification.

Tissue-specific gene regulation during development involves the interplay between transcription factors and epigenetic regulators binding to enhancer and promoter elements. The pattern of active enhancers defines the cellular differentiation state. However, developmental gene activation involves a previous step called chromatin priming which is not fully understood.

Transcriptional reprogramming by mutated IRF4 in lymphoma.

Disease-causing mutations in genes encoding transcription factors (TFs) can affect TF interactions with their cognate DNA-binding motifs. Whether and how TF mutations impact upon the binding to TF composite elements (CE) and the interaction with other TFs is unclear. Here, we report a distinct mechanism of TF alteration in human lymphomas with perturbed B cell identity, in particular classic Hodgkin lymphoma.

Identification and characterization of enhancer elements controlling cell type-specific and signalling dependent chromatin programming during hematopoietic development.

The development of multi-cellular organisms from a single fertilized egg requires to differentially execute the information encoded in our DNA. This complex process is regulated by the interplay of transcription factors with a chromatin environment, both of which provide the epigenetic information maintaining cell-type specific gene expression patterns. Moreover, transcription factors and their target genes form vast interacting gene regulatory networks which can be exquisitely stable.

A genome-wide relay of signalling-responsive enhancers drives hematopoietic specification.

Developmental control of gene expression critically depends on distal cis-regulatory elements including enhancers which interact with promoters to activate gene expression. To date no global experiments have been conducted that identify their cell type and cell stage-specific activity within one developmental pathway and in a chromatin context. Here, we describe a high-throughput method that identifies thousands of differentially active cis-elements able to stimulate a minimal promoter at five stages of hematopoietic progenitor development from embryonic stem (ES) cells, which can be adapted to any ES cell derived cell type.

The transcriptional regulation of normal and malignant blood cell development.

Development of multicellular organisms requires the differential usage of our genetic information to change one cell fate into another. This process drives the appearance of different cell types that come together to form specialized tissues sustaining a healthy organism. In the last decade, by moving away from studying single genes toward a global view of gene expression control, a revolution has taken place in our understanding of how genes work together and how cells communicate to translate the information encoded in the genome into a body plan.