ASXL1 interacts with the cohesin complex to maintain chromatid separation and gene expression for normal hematopoiesis

Zhaomin Li, Peng Zhang, Aimin Yan, Zhengyu Guo, Yuguang Ban, Jin Li, Shi Chen, Hui Yang, Yongzheng He, Jianping Li, Ying Guo, Wen Zhang, Ehsan Hajiramezanali, Huangda An, Darlene Fajardo, J. William Harbour, Yijun Ruan, Stephen D Nimer, Peng Yu, Xi ChenMingjiang Xu, Feng-Chun Yang

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

ASXL1 is frequently mutated in a spectrum of myeloid malignancies with poor prognosis. Loss of Asxl1 leads to myelodysplastic syndrome–like disease in mice; however, the underlying molecular mechanisms remain unclear. We report that ASXL1 interacts with the cohesin complex, which has been shown to guide sister chromatid segregation and regulate gene expression. Loss of Asxl1 impairs the cohesin function, as reflected by an impaired telophase chromatid disjunction in hematopoietic cells. Chromatin immunoprecipitation followed by DNA sequencing data revealed that ASXL1, RAD21, and SMC1A share 93% of genomic binding sites at promoter regions in LincKit+ (LK) cells. We have shown that loss of Asxl1 reduces the genome binding of RAD21 and SMC1A and alters the expression of ASXL1/cohesin target genes in LK cells. Our study underscores the ASXL1-cohesin interaction as a novel means to maintain normal sister chromatid separation and regulate gene expression in hematopoietic cells.

Original languageEnglish (US)
Article numbere1601602
JournalScience advances
Volume3
Issue number1
DOIs
StatePublished - Jan 1 2017

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Chromatids
Hematopoiesis
Gene Expression
Telophase
Chromatin Immunoprecipitation
DNA Sequence Analysis
Genetic Promoter Regions
Binding Sites
Genome
cohesins
Genes
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

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ASXL1 interacts with the cohesin complex to maintain chromatid separation and gene expression for normal hematopoiesis. / Li, Zhaomin; Zhang, Peng; Yan, Aimin; Guo, Zhengyu; Ban, Yuguang; Li, Jin; Chen, Shi; Yang, Hui; He, Yongzheng; Li, Jianping; Guo, Ying; Zhang, Wen; Hajiramezanali, Ehsan; An, Huangda; Fajardo, Darlene; William Harbour, J.; Ruan, Yijun; Nimer, Stephen D; Yu, Peng; Chen, Xi; Xu, Mingjiang; Yang, Feng-Chun.

In: Science advances, Vol. 3, No. 1, e1601602, 01.01.2017.

Research output: Contribution to journalArticle

Li, Z, Zhang, P, Yan, A, Guo, Z, Ban, Y, Li, J, Chen, S, Yang, H, He, Y, Li, J, Guo, Y, Zhang, W, Hajiramezanali, E, An, H, Fajardo, D, William Harbour, J, Ruan, Y, Nimer, SD, Yu, P, Chen, X, Xu, M & Yang, F-C 2017, 'ASXL1 interacts with the cohesin complex to maintain chromatid separation and gene expression for normal hematopoiesis', Science advances, vol. 3, no. 1, e1601602. https://doi.org/10.1126/sciadv.1601602
Li, Zhaomin ; Zhang, Peng ; Yan, Aimin ; Guo, Zhengyu ; Ban, Yuguang ; Li, Jin ; Chen, Shi ; Yang, Hui ; He, Yongzheng ; Li, Jianping ; Guo, Ying ; Zhang, Wen ; Hajiramezanali, Ehsan ; An, Huangda ; Fajardo, Darlene ; William Harbour, J. ; Ruan, Yijun ; Nimer, Stephen D ; Yu, Peng ; Chen, Xi ; Xu, Mingjiang ; Yang, Feng-Chun. / ASXL1 interacts with the cohesin complex to maintain chromatid separation and gene expression for normal hematopoiesis. In: Science advances. 2017 ; Vol. 3, No. 1.
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AU - William Harbour, J.

AU - Ruan, Yijun

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AU - Yu, Peng

AU - Chen, Xi

AU - Xu, Mingjiang

AU - Yang, Feng-Chun

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AB - ASXL1 is frequently mutated in a spectrum of myeloid malignancies with poor prognosis. Loss of Asxl1 leads to myelodysplastic syndrome–like disease in mice; however, the underlying molecular mechanisms remain unclear. We report that ASXL1 interacts with the cohesin complex, which has been shown to guide sister chromatid segregation and regulate gene expression. Loss of Asxl1 impairs the cohesin function, as reflected by an impaired telophase chromatid disjunction in hematopoietic cells. Chromatin immunoprecipitation followed by DNA sequencing data revealed that ASXL1, RAD21, and SMC1A share 93% of genomic binding sites at promoter regions in Lin−cKit+ (LK) cells. We have shown that loss of Asxl1 reduces the genome binding of RAD21 and SMC1A and alters the expression of ASXL1/cohesin target genes in LK cells. Our study underscores the ASXL1-cohesin interaction as a novel means to maintain normal sister chromatid separation and regulate gene expression in hematopoietic cells.

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