Novel binding partners of Ldb1 are required for haematopoietic development.
Ldb1, a ubiquitously expressed LIM domain binding protein, is essential in a number of tissues during development. It interacts with Gata1, Tal1, E2A and Lmo2 to form a transcription factor complex regulating late erythroid genes. We identify a number of novel Ldb1 interacting proteins in erythroleukaemic cells, in particular the repressor protein Eto-2 (and its family member Mtgr1), the cyclin-dependent kinase Cdk9, and the bridging factor Lmo4. MO-mediated knockdowns in zebrafish show these factors to be essential for definitive haematopoiesis. In accordance with the zebrafish results these factors are coexpressed in prehaematopoietic cells of the early mouse embryo, although we originally identified the complex in late erythroid cells. Based on the change in subcellullar localisation of Eto-2 we postulate that it plays a central role in the transition from the migration and expansion phase of the prehaematopoietic cells to the establishment of definitive haematopoietic stem cells.
Meier
Natalia
N
Department of Cell Biology and Genetics, Erasmus MC, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Krpic
Sanja
S
Rodriguez
Patrick
P
Strouboulis
John
J
Monti
Maria
M
Krijgsveld
Jeroen
J
Gering
Martin
M
Patient
Roger
R
Hostert
Arnd
A
Grosveld
Frank
F
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D042863:Cyclin-Dependent Kinase 9 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D041905:Erythroid Cells / Q000166:cytology; D004920:Erythropoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D060588:LIM Domain Proteins; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C117411:Cbfa2t3 protein, mouse; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; C102084:Ldb1 protein, mouse; C491976:Lmo4 protein, mouse; D009687:Nuclear Proteins; D012097:Repressor Proteins; C517154:Tcf4 protein, zebrafish; D000073940:Transcription Factor 4; D014157:Transcription Factors; D029961:Zebrafish Proteins; C486313:ldb1a protein, zebrafish; C467972:Cdk9 protein, mouse; C517155:Cdk9 protein, zebrafish; D042863:Cyclin-Dependent Kinase 9