A requirement for Lim domain binding protein 1 in erythropoiesis.
During erythrocyte development, the nuclear cofactor Lim domain binding protein 1 (Ldb1) functions as a core subunit of multiprotein DNA binding complexes that include the transcription factors Scl and Gata-1 and the Lim-only adapter Lmo2. Scl, Gata-1, and Lmo2 are each required for erythropoiesis, suggesting that Ldb1-nucleated transcription complexes regulate key steps during erythropoiesis. We documented a requirement for Ldb1 in erythropoiesis in mice. Analysis of ldb1(-/-) embryos revealed a critical requirement for Ldb1 during primitive erythropoiesis, and conditional inactivation of ldb1 at later stages of gestation and in adult mice demonstrated that Ldb1 is continuously required for both definitive erythropoiesis and megakaryopoiesis. Down-regulation of Ldb1 in erythroblasts inhibited the expression of multiple erythroid-specific and prosurvival genes. These results represent the first unequivocal demonstration of a role for Ldb1 in erythropoiesis in vivo and establish a critical function for Ldb1-nucleated complexes in regulating the erythroid/megakaryocyte transcriptional program.
Section on Cellular and Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
LiQi
L
Li
Jan Y
JY
Lee
Jennifer
J
Gross
Sang-Hyun
SH
Song
Ann
A
Dean
Paul E
PE
Love
D000818:Animals; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000502:physiology*; D004920:Erythropoiesis; D005786:Gene Expression Regulation; D060588:LIM Domain Proteins; D008533:Megakaryocytes / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic
D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C102084:Ldb1 protein, mouse