title: Ldb1 complexes: the new master regulators of erythroid gene transcription.
abstract: Elucidation of the genetic pathways that control red blood cell development has been a central goal of erythropoiesis research over the past decade. Notably, data from several recent studies have provided new insights into the regulation of erythroid gene transcription. Transcription profiling demonstrates that erythropoiesis is mainly controlled by a small group of lineage-restricted transcription factors [Gata binding protein 1 (Gata1), T cell acute lymphocytic leukemia 1 protein (Tal1), and Erythroid Kruppel-like factor (EKLF; henceforth referred to as Klf1)]. Binding-site mapping using ChIP-Seq indicates that most DNA-bound Gata1 and Tal1 proteins are contained within higher order complexes (Ldb1 complexes) that include the nuclear adapters Ldb1 and Lmo2. Ldb1 complexes regulate Klf1, and Ldb1 complex-binding sites frequently colocalize with Klf1 at erythroid genes and cis-regulatory elements, indicating strong functional synergy between Gata1, Tal1, and Klf1. Together with new data demonstrating that Ldb1 can mediate long-range promoter-enhancer interactions, these findings provide a foundation for the first comprehensive models of the global regulation of erythroid gene transcription.
authors.affiliation: Eunice Kennedy Shriver, National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: lovep@mail.nih.gov.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Love
authors.affiliation: Eunice Kennedy Shriver, National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Claude
authors.initials: C
authors.lastname: Warzecha
authors.affiliation: Eunice Kennedy Shriver, National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: LiQi
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D063185:Epigenetic Repression; D004920:Erythropoiesis / Q000235:genetics*; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D023421:Models, Animal; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D050982:GATA1 Transcription Factor; D051741:Kruppel-Like Transcription Factors; D060588:LIM Domain Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C494689:Gata1 protein, mouse; C102084:Ldb1 protein, mouse; C489366:Tal1 protein, mouse; C080774:erythroid Kruppel-like factor
keywords: ChIP-Seq; Gata1; Klf1; Ldb1 complexes; Tal1; erythropoiesis; transcriptional regulation