title: ASXL1 interacts with the cohesin complex to maintain chromatid separation and gene expression for normal hematopoiesis.
abstract: ASXL1is frequently mutated in a spectrum of myeloid malignancies with poor prognosis. Loss ofAsxl1leads 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 ofAsxl1impairs 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 ofAsxl1reduces 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.
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: Li
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Aimin
authors.initials: A
authors.lastname: Yan
authors.affiliation: Department of Electrical and Computer Engineering and TEES-AgriLife Center for Bioinformatics and Genomic Systems Engineering, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Ban
authors.affiliation: Department of Electrical and Computer Engineering and TEES-AgriLife Center for Bioinformatics and Genomic Systems Engineering, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Shi
authors.initials: S
authors.lastname: Chen
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Yongzheng
authors.initials: Y
authors.lastname: He
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Jianping
authors.initials: J
authors.lastname: Li
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Electrical and Computer Engineering and TEES-AgriLife Center for Bioinformatics and Genomic Systems Engineering, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Hajiramezanali
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Huangda
authors.initials: H
authors.lastname: An
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Darlene
authors.initials: D
authors.lastname: Fajardo
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: J William
authors.initials: JW
authors.lastname: Harbour
authors.affiliation: The Jackson Laboratory for Genomic Medicine, Farmington, CT 06030, USA.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.; Department of Internal Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Nimer
authors.affiliation: Department of Electrical and Computer Engineering and TEES-AgriLife Center for Bioinformatics and Genomic Systems Engineering, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.; Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Mingjiang
authors.initials: M
authors.lastname: Xu
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Feng-Chun
authors.identifier: 0000-0001-8524-4095
authors.initials: FC
authors.lastname: Yang
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002842:Chromatids / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation / Q000502:physiology*; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation / Q000502:physiology*; D006410:Hematopoiesis / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013692:Telophase / Q000502:physiology; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012097:Repressor Proteins; D000097722:Cohesins; C510915:Asxl1 protein, mouse; C465862:Rad21 protein, mouse
keywords: ASXL1; cohesin complex; gene regulation; hematopoiesis