TY - JOUR
T1 - A novel complex, RUNX1-MYEF2, represses hematopoietic genes in erythroid cells
AU - van Riel, Boet
AU - Pakozdi, Tibor
AU - Brouwer, Rutger
AU - Monteiro, Rui
AU - Tuladhar, Kapil
AU - Franke, Vedran
AU - Bryne, Jan Christian
AU - Jorna, Ruud
AU - Rijkers, Erik Jan
AU - van Ijcken, Wilfred
AU - Andrieu-Soler, Charlotte
AU - Demmers, Jeroen
AU - Patient, Roger
AU - Soler, Eric
AU - Lenhard, Boris
AU - Grosveld, Frank
PY - 2012/10/1
Y1 - 2012/10/1
N2 - RUNX1 is known to be an essential transcription factor for generating hematopoietic stem cells (HSC), but much less is known about its role in the downstream process of hematopoietic differentiation. RUNX1 has been shown to be part of a large transcription factor complex, together with LDB1, GATA1, TAL1, and ETO2 (N. Meier et al., Development 133:4913- 4923, 2006) in erythroid cells. We used a tagging strategy to show that RUNX1 interacts with two novel protein partners, LSD1 and MYEF2, in erythroid cells. MYEF2 is bound in undifferentiated cells and is lost upon differentiation, whereas LSD1 is bound in differentiated cells. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) and microarray expression analysis were used to show that RUNX1 binds approximately 9,000 target sites in erythroid cells and is primarily active in the undifferentiated state. Functional analysis shows that a subset of the target genes is suppressed by RUNX1 via the newly identified partner MYEF2. Knockdown of Myef2 expression in developing zebrafish results in a reduced number of HSC.
AB - RUNX1 is known to be an essential transcription factor for generating hematopoietic stem cells (HSC), but much less is known about its role in the downstream process of hematopoietic differentiation. RUNX1 has been shown to be part of a large transcription factor complex, together with LDB1, GATA1, TAL1, and ETO2 (N. Meier et al., Development 133:4913- 4923, 2006) in erythroid cells. We used a tagging strategy to show that RUNX1 interacts with two novel protein partners, LSD1 and MYEF2, in erythroid cells. MYEF2 is bound in undifferentiated cells and is lost upon differentiation, whereas LSD1 is bound in differentiated cells. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) and microarray expression analysis were used to show that RUNX1 binds approximately 9,000 target sites in erythroid cells and is primarily active in the undifferentiated state. Functional analysis shows that a subset of the target genes is suppressed by RUNX1 via the newly identified partner MYEF2. Knockdown of Myef2 expression in developing zebrafish results in a reduced number of HSC.
UR - http://www.scopus.com/inward/record.url?scp=84868697416&partnerID=8YFLogxK
U2 - 10.1128/MCB.05938-11
DO - 10.1128/MCB.05938-11
M3 - Article
C2 - 22801375
AN - SCOPUS:84868697416
SN - 0270-7306
VL - 32
SP - 3814
EP - 3822
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 19
ER -