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The transcriptional regulation of normal and malignant blood cell development

Journal

FEBS JOURNAL
Volume 289, Issue 5, Pages 1240-1255

Publisher

WILEY
DOI: 10.1111/febs.15735

Keywords

acute myeloid leukemia; gene regulatory networks; hematopoiesis; nuclear compartments; transcription and chromatin

Funding

  1. Biotechnology and Biological Sciences Research Council, UK
  2. Medical Research Council, UK
  3. Blood Cancer, UK
  4. BBSRC [BB/R014809/1] Funding Source: UKRI
  5. MRC [MR/S021469/1] Funding Source: UKRI

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The development of multicellular organisms involves differential usage of genetic information to generate various cell types that form specialized tissues. A shift from studying single genes to a global view of gene expression control has revolutionized our understanding of gene functions and cell communication. The paradigm of blood cell development highlights how transcription factors and chromatin components work together in shaping gene regulatory networks and driving differentiation, as well as how this process is altered in blood cancers. Emerging concepts place these processes within subnuclear structures, adding another layer of control to differential gene expression.
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. The development of hematopoietic cells has long served as a paradigm of development in general. In this review, we highlight how transcription factors and chromatin components work together to shape the gene regulatory networks controlling gene expression in the hematopoietic system and to drive blood cell differentiation. In addition, we outline how this process goes astray in blood cancers. We also touch upon emerging concepts that place these processes firmly into their associated subnuclear structures adding another layer of the control of differential gene expression.

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