CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation

Jingmei Hsu; Hsuan Ting Huang; Chung Tsai Lee; Avik Choudhuri; Nicola K. Wilson; Brian J. Abraham; Victoria Moignard; Iwo Kucinski; Shuqian Yu; R. Katherine Hyde; Joanna Tober; Xiongwei Cai; Yan Li; Yalin Guo; Song Yang; Michael Superdock; Eirini Trompouki; Fernando J. Calero-Nieto; Ghamari Alireza; Jing Jiang; Peng Gao; Long Gao; Vy Nguyen; Anne L. Robertson; Ellen M. Durand; Katie L. Kathrein; Iannis Aifantis; Scott A. Gerber; Wei Tong; Kai Tan; Alan B. Cantor; Yi Zhou; P. Paul Liu; Richard A. Young; Berthold Göttgens; Nancy A. Speck; Leonard I. Zon

doi:10.1073/pnas.2003228117

CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation

Jingmei Hsu, Hsuan Ting Huang, Chung Tsai Lee, Avik Choudhuri, Nicola K. Wilson, Brian J. Abraham, Victoria Moignard, Iwo Kucinski, Shuqian Yu, R. Katherine Hyde, Joanna Tober, Xiongwei Cai, Yan Li, Yalin Guo, Song Yang, Michael Superdock, Eirini Trompouki, Fernando J. Calero-Nieto, Ghamari Alireza, Jing JiangPeng Gao, Long Gao, Vy Nguyen, Anne L. Robertson, Ellen M. Durand, Katie L. Kathrein, Iannis Aifantis, Scott A. Gerber, Wei Tong, Kai Tan, Alan B. Cantor, Yi Zhou, P. Paul Liu, Richard A. Young, Berthold Göttgens, Nancy A. Speck, Leonard I. Zon

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

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.

Original language	English (US)
Pages (from-to)	23626-23635
Number of pages	10
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	117
Issue number	38
DOIs	https://doi.org/10.1073/pnas.2003228117
State	Published - Sep 22 2020
Externally published	Yes

Keywords

CHD7
Hematopoiesis
RUNX1

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.2003228117

Cite this

Hsu, J., Huang, H. T., Lee, C. T., Choudhuri, A., Wilson, N. K., Abraham, B. J., Moignard, V., Kucinski, I., Yu, S., Hyde, R. K., Tober, J., Cai, X., Li, Y., Guo, Y., Yang, S., Superdock, M., Trompouki, E., Calero-Nieto, F. J., Alireza, G., ... Zon, L. I. (2020). CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation. Proceedings of the National Academy of Sciences of the United States of America, 117(38), 23626-23635. https://doi.org/10.1073/pnas.2003228117

Hsu, J, Huang, HT, Lee, CT, Choudhuri, A, Wilson, NK, Abraham, BJ, Moignard, V, Kucinski, I, Yu, S, Hyde, RK, Tober, J, Cai, X, Li, Y, Guo, Y, Yang, S, Superdock, M, Trompouki, E, Calero-Nieto, FJ, Alireza, G, Jiang, J, Gao, P, Gao, L, Nguyen, V, Robertson, AL, Durand, EM, Kathrein, KL, Aifantis, I, Gerber, SA, Tong, W, Tan, K, Cantor, AB, Zhou, Y, Liu, PP, Young, RA, Göttgens, B, Speck, NA & Zon, LI 2020, 'CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation', Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 38, pp. 23626-23635. https://doi.org/10.1073/pnas.2003228117

@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.}",

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",

}

TY - JOUR

T1 - CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation

AU - Hsu, Jingmei

AU - Huang, Hsuan Ting

AU - Lee, Chung Tsai

AU - Choudhuri, Avik

AU - Wilson, Nicola K.

AU - Abraham, Brian J.

AU - Moignard, Victoria

AU - Kucinski, Iwo

AU - Yu, Shuqian

AU - Hyde, R. Katherine

AU - Tober, Joanna

AU - Cai, Xiongwei

AU - Li, Yan

AU - Guo, Yalin

AU - Yang, Song

AU - Superdock, Michael

AU - Trompouki, Eirini

AU - Calero-Nieto, Fernando J.

AU - Alireza, Ghamari

AU - Jiang, Jing

AU - Gao, Peng

AU - Gao, Long

AU - Nguyen, Vy

AU - Robertson, Anne L.

AU - Durand, Ellen M.

AU - Kathrein, Katie L.

AU - Aifantis, Iannis

AU - Gerber, Scott A.

AU - Tong, Wei

AU - Tan, Kai

AU - Cantor, Alan B.

AU - Zhou, Yi

AU - Liu, P. Paul

AU - Young, Richard A.

AU - Göttgens, Berthold

AU - Speck, Nancy A.

AU - Zon, Leonard I.

PY - 2020/9/22

Y1 - 2020/9/22

N2 - 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.

AB - 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.

KW - CHD7

KW - Hematopoiesis

KW - RUNX1

UR - http://www.scopus.com/inward/record.url?scp=85091584596&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85091584596&partnerID=8YFLogxK

U2 - 10.1073/pnas.2003228117

DO - 10.1073/pnas.2003228117

M3 - Article

C2 - 32883883

AN - SCOPUS:85091584596

SN - 0027-8424

VL - 117

SP - 23626

EP - 23635

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 38

ER -

CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this