Discordant regulation of SCL/TAL-1 mRNA and protein during erythroid differentiation.
AffiliationUniversity of Cambridge, Department of Haematology, MRC Centre, UK.
MetadataShow full item record
AbstractThe SCL/TAL1 gene was originally identified by virtue of its rearrangement and transcriptional activation in patients with T cell acute lymphoblastic leukaemia. It encodes a helix-loop-helix transcription factor, is not normally expressed in T cells, but is expressed in erythroid, mast, megakaryocytic and progenitor cells. Over-expression of sense and antisense constructs have implicated SCL as a positive regulator of erythroid differentiation. In addition we have previously shown that SCL mRNA levels undergo biphasic modulation during induced erythroid differentiation of murine erythroleukaemia (MEL) cells with a transient early fall followed by a late rise. In this paper we have studied expression of the SCL protein during erythroid differentiation and also the molecular basis for the raised SCL mRNA levels that accompany erythroid differentiation. We have generated an anti-SCL antiserum and used it to demonstrate that an early transient fall in SCL protein does not occur during induced differentiation of MEL cells. Furthermore SCL protein levels underwent a late fall in three different models of erythroid differentiation and in two models of myeloid differentiation. The fall in SCL protein levels during induced erythroid differentiation contrasted with the concomitant marked rise in SCL mRNA levels. These observations have significant implications for the mechanism by which SCL may regulate erythropoiesis. In addition we have demonstrated that the stability of SCL mRNA was only marginally enhanced during erythroid differentiation of MEL cells, whereas the activity of a luciferase reporter construct driven by the SCL promoter was increased 11- to 17-fold. Up-regulation of transcription therefore accounted for most of the increase in SCL mRNA levels during erythroid differentiation.
CitationDiscordant regulation of SCL/TAL-1 mRNA and protein during erythroid differentiation. 1995, 11 (1):131-9 Oncogene
- Lineage-restricted regulation of the murine SCL/TAL-1 promoter.
- Authors: Bockamp EO, McLaughlin F, Murrell AM, Göttgens B, Robb L, Begley CG, Green AR
- Issue date: 1995 Aug 15
- SCL is coexpressed with GATA-1 in hemopoietic cells but is also expressed in developing brain.
- Authors: Green AR, Lints T, Visvader J, Harvey R, Begley CG
- Issue date: 1992 Apr
- The SCL gene product: a positive regulator of erythroid differentiation.
- Authors: Aplan PD, Nakahara K, Orkin SH, Kirsch IR
- Issue date: 1992 Nov
- Antisense SCL suppresses self-renewal and enhances spontaneous erythroid differentiation of the human leukaemic cell line K562.
- Authors: Green AR, DeLuca E, Begley CG
- Issue date: 1991 Dec
- Distinct mechanisms direct SCL/tal-1 expression in erythroid cells and CD34 positive primitive myeloid cells.
- Authors: Bockamp EO, McLaughlin F, Göttgens B, Murrell AM, Elefanty AG, Green AR
- Issue date: 1997 Mar 28