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 Chen; Mingjiang Xu; Feng-Chun Yang

doi:10.1126/sciadv.1601602

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

Journal article

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Peer reviewed

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, …

Science advances, Vol.3(1), pp.e1601602-e1601602

2017-01

DOI: https://doi.org/10.1126/sciadv.1601602

PMCID: PMC5249256

PMID: 28116354

Abstract

Chromosomal Proteins, Non-Histone - metabolism

Chromatids - genetics

Cell Cycle Proteins - metabolism

Gene Expression Regulation - physiology

Repressor Proteins - genetics

Nuclear Proteins - metabolism

Phosphoproteins - genetics

Phosphoproteins - metabolism

Chromosomal Proteins, Non-Histone - genetics

Mice, Knockout

Chromatids - metabolism

Animals

Cell Cycle Proteins - genetics

Chromosome Segregation - physiology

Hematopoiesis - physiology

Mice

Telophase - physiology

Nuclear Proteins - genetics

Repressor Proteins - metabolism

is frequently mutated in a spectrum of myeloid malignancies with poor prognosis. Loss of 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 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 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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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.103 Blood Disorders; 1.103.155 Acute Myeloid Leukemia
Web Of Science research areas: Cell Biology
ESI research areas: Molecular Biology & Genetics

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Title: ASXL1 interacts with the cohesin complex to maintain chromatid separation and gene expression for normal hematopoiesis
Creators: Zhaomin Li - 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
Peng Zhang - 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
Aimin Yan - Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
Zhengyu Guo - 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
Yuguang Ban - Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
Jin Li - 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
Shi Chen - 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
Hui Yang - 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
Yongzheng He - Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Jianping Li - 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
Ying Guo - 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
Wen Zhang - 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
Ehsan Hajiramezanali - 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
Huangda An - 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
Darlene Fajardo - 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
J William Harbour - Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
Yijun Ruan - The Jackson Laboratory for Genomic Medicine, Farmington, CT 06030, USA
Stephen D Nimer - 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
Peng Yu - 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
Xi Chen - 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
Mingjiang Xu - 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
Feng-Chun Yang - 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
Publication Details: Science advances, Vol.3(1), pp.e1601602-e1601602
Publisher: United States
Grant note: R01 CA161870 / NCI NIH HHS R21 CA185751 / NCI NIH HHS U54 DK107967 / NIDDK NIH HHS UM1 HG009409 / NHGRI NIH HHS P30 CA034196 / NCI NIH HHS R01 CA172408 / NCI NIH HHS R01 CA186714 / NCI NIH HHS R01 CA166835 / NCI NIH HHS R25 HG007631 / NHGRI NIH HHS
Academic Unit: UMMG Dept of Dermatology & Cutaneous Surgery; Miller School of Medicine; Leadership Department; MHBS - Business Technology; Sylvester Comprehensive Cancer Center; UMMG Department of Public Health Sciences Research; Miami Herbert Business School; UMMG Department of Ophthalmology
Language: English
Resource Type: Journal article
PMID: 28116354
PMCID: PMC5249256
Record Identifier: 991031577552302976