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Adrian J C Bloor

Publications and source records attributed to Adrian J C Bloor.

5 recordsLinked to original sources
PubMed2005

RFP represses transcriptional activation by bHLH transcription factors.

Basic helix-loop-helix (bHLH) transcription factors play a pivotal role in the regulation of tumorigenesis, and also in a wide range of other developmental processes in diverse species from yeast to humans. Here we demonstrate for the first time that Ret finger protein (RFP), a member of the TRIM family of proteins initially identified as a recombined transforming gene from a human lymphoma, is a novel interaction partner for four different bHLH proteins (SCL, E47, MyoD and mASH-1), but does not interact with GATA-1 or PU.1. Interaction with SCL required the B-box and first coiled-coil region of RFP together with the bHLH domain of SCL. RFP was able to repress transcriptional activation by E47, MyoD and mASH-1, but not by members of several other transcription factor families. Transcriptional repression by RFP was trichostatin A sensitive and did not involve an Id-like mechanism or ubiquitination with subsequent degradation of bHLH proteins. Instead, our results suggest that bHLH transcription factors are regulated by a previously undescribed interaction with RFP, which functions to recruit HDAC and/or Polycomb proteins and thus repress target genes of bHLH proteins. These results reveal an unexpected link between the bHLH and TRIM protein families.

Animals↗
PubMed2002

Rescue of the lethal scl(-/-) phenotype by the human SCL locus.

The stem cell leukemia (SCL) gene encodes a basic helix-loop-helix transcription factor with a critical role in the development of both blood and endothelium. Loss-of-function studies have shown that SCL is essential for the formation of hematopoietic stem cells, for subsequent erythroid development and for yolk sac angiogenesis. SCL exhibits a highly conserved pattern of expression from mammals to teleost fish. Several murine SCL enhancers have been identified, each of which directs reporter gene expression in vivo to a subdomain of the normal SCL expression pattern. However, regulatory elements necessary for SCL expression in erythroid cells remain to be identified and the size of the chromosomal domain needed to support appropriate SCL transcription is unknown. Here we demonstrate that a 130-kilobase (kb) yeast artificial chromosome (YAC) containing the human SCL locus completely rescued the embryonic lethal phenotype of scl(-/-) mice. Rescued YAC(+) scl(-/-) mice were born in appropriate Mendelian ratios, were healthy and fertile, and exhibited no detectable abnormality of yolk sac, fetal liver, or adult hematopoiesis. The human SCL protein can therefore substitute for its murine homologue. In addition, our results demonstrate that the human SCL YAC contains the chromosomal domain necessary to direct expression to the erythroid lineage and to all other tissues in which SCL performs a nonredundant essential function.

Animals↗
PubMed2002

The role of the stem cell leukemia (SCL) gene in hematopoietic and endothelial lineage specification.

Anatomical observations made at the beginning of the twentieth century revealed an intimate association between the ontogeny of blood and endothelium and led to the hypothesis of a common cell of origin termed the hemangioblast. However, the precise nature of the cellular intermediates involved in the development of both lineages from uncommitted precursors to mature cell types is still the subject of ongoing studies, as are the molecular mechanisms driving this process. There is clear evidence that lineage-restricted transcription factors play a central role in the genesis of mature lineage committed cells from multipotent progenitors. Amongst these, the basic helix-loop-helix (bHLH) family is of key importance for cell fate determination in the development of the hematopoietic system and beyond. This article will review the current evidence for the common origin of blood and endothelium, focusing on the function of the bHLH protein encoded by the stem cell leukemia (SCL) gene, and its role as a pivotal regulator of hematopoiesis and vasculogenesis.

Basic Helix-Loop-Helix Proteins↗