Ldb1 complexes globally regulate Gata-1 dependent erythroid gene expression

Tuesday, October 09, 2012 — Poster Session I
1:00 p.m. – 3:00 p.m	Natcher Conference Center, Building 45	NICHD	BIOINFO-11

Authors

• L Li
• J Freudenberg
• K Cui
• S-H Song
• A Dean
• K Zhao
• R Jothi
• P.E. Love

Abstract

In erythroid cells, the nuclear adapter LIM domain binding protein 1 (Ldb1) functions as a core subunit of a multiprotein DNA binding complex that includes the transcription factors Scl, Gata-1 and the LIM only adapter Lmo2. Scl, Gata-1 and Lmo2 are each required for erythropoiesis suggesting the possibility that these proteins function cooperatively within Ldb1 complexes to regulate key steps in erythroid development. Our previous studies have shown Ldb1 is required for erythropoiesis (Li et al., J. Exp. Med. 2010) and is essential for fetal and adult hematopoietic stem cell maintenance (Li et al., Nat. Immunol. 2011). In this study, we examined: 1) the binding of Ldb1 complexes at erythroid genes using genome-wide profiling by Chip-Seq and 2) the requirement for Ldb1 for expression of these genes by shRNA-mediated knockdown of Ldb1 in erythroid cell lines. Our results identified Ldb1 complex-binding sites at highly conserved regions in promoter and known regulatory elements of many key erythroid genes. In addition, knockdown of Ldb1 resulted in the down-regulation of many erythroid and megakaryocyte specific genes. These results represent a comprehensive demonstration of the role for Ldb1 in erythropoiesis and advocate a critical function for Ldb1-nucleated complexes in regulating the erythroid/megakaryocyte transcriptional program.

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