@article{cf2eceb845664442957eec72218f6672,
title = "CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation",
abstract = "Hematopoietic stem and progenitor cell (HSPC) formation and lineage differentiation involve gene expression programs orchestrated by transcription factors and epigenetic regulators. Genetic disruption of the chromatin remodeler chromodomain-helicase-DNA-binding protein 7 (CHD7) expanded phenotypic HSPCs, erythroid, and myeloid lineages in zebrafish and mouse embryos. CHD7 acts to suppress hematopoietic differentiation. Binding motifs for RUNX and other hematopoietic transcription factors are enriched at sites occupied by CHD7, and decreased RUNX1 occupancy correlated with loss of CHD7 localization. CHD7 physically interacts with RUNX1 and suppresses RUNX1-induced expansion of HSPCs during development through modulation of RUNX1 activity. Consequently, the RUNX1:CHD7 axis provides proper timing and function of HSPCs as they emerge during hematopoietic development or mature in adults, representing a distinct and evolutionarily conserved control mechanism to ensure accurate hematopoietic lineage differentiation.",
keywords = "CHD7, Hematopoiesis, RUNX1",
author = "Jingmei Hsu and Huang, {Hsuan Ting} and Lee, {Chung Tsai} and Avik Choudhuri and Wilson, {Nicola K.} and Abraham, {Brian J.} and Victoria Moignard and Iwo Kucinski and Shuqian Yu and Hyde, {R. Katherine} and Joanna Tober and Xiongwei Cai and Yan Li and Yalin Guo and Song Yang and Michael Superdock and Eirini Trompouki and Calero-Nieto, {Fernando J.} and Ghamari Alireza and Jing Jiang and Peng Gao and Long Gao and Vy Nguyen and Robertson, {Anne L.} and Durand, {Ellen M.} and Kathrein, {Katie L.} and Iannis Aifantis and Gerber, {Scott A.} and Wei Tong and Kai Tan and Cantor, {Alan B.} and Yi Zhou and Liu, {P. Paul} and Young, {Richard A.} and Berthold G{\"o}ttgens and Speck, {Nancy A.} and Zon, {Leonard I.}",
note = "Funding Information: ACKNOWLEDGMENTS. We thank A. D. Yzaguirre for technical assistance with confocal microscopy, C.-Y. Tsai for help with identifying Runx1-interacting proteins, T. Gao and M. Matthews for help with ES cell culture, J. Tobias for help with IPA microarray data analysis, and C. Lobry for help with heatmap visualization of microarray data. We also thank the I. Aifantis, H. Knaut, J. Torres-Vasquez, and R.M. White laboratories in New York for use of laboratory and fish facility space to complete this work. This work was supported by NIH Grants R01 HL089969, R01 HL091724, and U01HL100405 (to N.A.S.); R01 HL04880, PPG-P015PO1HL32262-32, 5P30 DK49216, 5R01 DK53298, 5U01 HL10001-05, and R24 DK092760 (to L.I.Z.); and R01 HG002668 (to R.A.Y.). R.K.H. and P.P.L. are supported by the Intramural Research Program of the National Human Genome Research Institute and NIH Grant 4R00CA148963 (to R.K.H.). N.K.W., V.M., F.J.C.-N., and B.G. were supported by Bloodwise Grant 12029, Leukemia and Lymphoma Society Grant 7001-12, Cancer Research UK Grant C1163/A12765, and core infrastructure support by the Medical Research Council (MRC) of the Wellcome Trust and MRC Cambridge Stem Cell Institute Grant 097922/Z/11/Z. J.H. was supported by NIH Grants 5-T32-HL-007439-34 and K12CA076931. H.-T.H. was supported by NYSTEM Training Grant C026880. L.I.Z. is an Investigator of the Howard Hughes Medical Institute. Funding Information: We thank A. D. Yzaguirre for technical assistance with confocal microscopy, C.-Y. Tsai for help with identifying Runx1- interacting proteins, T. Gao and M. Matthews for help with ES cell culture, J. Tobias for help with IPA microarray data analysis, and C. Lobry for help with heatmap visualization of microarray data. We also thank the I. Aifantis, H. Knaut, J. Torres-Vasquez, and R.M. White laboratories in New York for use of laboratory and fish facility space to complete this work. This work was supported by NIH Grants R01 HL089969, R01 HL091724, and U01HL100405 (to N.A.S.); R01 HL04880, PPG-P015PO1HL32262-32, 5P30 DK49216, 5R01 DK53298, 5U01 HL10001-05, and R24 DK092760 (to L.I.Z.); and R01 HG002668 (to R.A.Y.). R.K.H. and P.P.L. are supported by the Intramural Research Program of the National Human Genome Research Institute and NIH Grant 4R00CA148963 (to R.K.H.). N.K.W., V.M., F.J.C.-N., and B.G. were supported by Bloodwise Grant 12029, Leukemia and Lymphoma Society Grant 7001-12, Cancer Research UK Grant C1163/A12765, and core infrastructure support by the Medical Research Council (MRC) of the Wellcome Trust and MRC Cambridge Stem Cell Institute Grant 097922/Z/11/Z. J.H. was supported by NIH Grants 5-T32-HL-007439-34 and K12CA076931. H.-T.H. was supported by NYSTEM Training Grant C026880. L.I.Z. is an Investigator of the Howard Hughes Medical Institute. Publisher Copyright: {\textcopyright} 2020 National Academy of Sciences. All rights reserved.",
year = "2020",
month = sep,
day = "22",
doi = "10.1073/pnas.2003228117",
language = "English (US)",
volume = "117",
pages = "23626--23635",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "38",
}