TY - JOUR
T1 - The scl+19 cell enhancer is not required for haematopoiesis: identification of a second bifunctional hematopoietic/endothelial enhancer regulated by Fil-1 and Elf-1
AU - Gottgens, B
AU - Broccardo, C
AU - Sanchez, M-J
AU - Deveaux, S
AU - Murphy, George
AU - Gothert, J
AU - Kotsopouloul, E
AU - Kinston, S
AU - Delaney, E
AU - Piltz, S
AU - Barton, LM
AU - Knezevic, K
AU - Erber, WN
AU - Begley, CG
AU - Frampton, Jonathan
AU - Green, AR
PY - 2004/1/1
Y1 - 2004/1/1
N2 - Analysis of cis-regulatory elements is central to understanding the genomic program for development. The scl/tal-1 transcription factor is essential for lineage commitment to blood cell formation and previous studies identified an scl enhancer (the +18/19 element) which was sufficient to target the vast majority of hematopoietic stem cells, together with hematopoietic progenitors and endothelium. Moreover, expression of scl under control of the +18/19 enhancer rescued blood progenitor formation in scl(-/-) embryos. However, here we demonstrate by using a knockout approach that, within the endogenous scl locus, the + 18/19 enhancer is not necessary for the initiation of set transcription or for the formation of hematopoietic cells. These results led to the identification of a bifunctional 5' enhancer (-3.8 element), which targets expression to hematopoietic progenitors and endothelium, contains conserved critical Ets sites, and is bound by Ets family transcription factors, including Fli-1 and Elf-1. These data demonstrate that two geographically distinct but functionally related enhancers regulate scl transcription in hematopoietic progenitors and endothelial cells and suggest that enhancers with dual hematopoietic-endothelial activity may represent a general strategy for regulating blood and endothelial development.
AB - Analysis of cis-regulatory elements is central to understanding the genomic program for development. The scl/tal-1 transcription factor is essential for lineage commitment to blood cell formation and previous studies identified an scl enhancer (the +18/19 element) which was sufficient to target the vast majority of hematopoietic stem cells, together with hematopoietic progenitors and endothelium. Moreover, expression of scl under control of the +18/19 enhancer rescued blood progenitor formation in scl(-/-) embryos. However, here we demonstrate by using a knockout approach that, within the endogenous scl locus, the + 18/19 enhancer is not necessary for the initiation of set transcription or for the formation of hematopoietic cells. These results led to the identification of a bifunctional 5' enhancer (-3.8 element), which targets expression to hematopoietic progenitors and endothelium, contains conserved critical Ets sites, and is bound by Ets family transcription factors, including Fli-1 and Elf-1. These data demonstrate that two geographically distinct but functionally related enhancers regulate scl transcription in hematopoietic progenitors and endothelial cells and suggest that enhancers with dual hematopoietic-endothelial activity may represent a general strategy for regulating blood and endothelial development.
UR - http://www.scopus.com/inward/record.url?scp=2942526253&partnerID=8YFLogxK
U2 - 10.1128/MCB.24.5.1870-1883.2004
DO - 10.1128/MCB.24.5.1870-1883.2004
M3 - Article
C2 - 14966269
SN - 1098-5549
VL - 24
SP - 1870
EP - 1883
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
ER -