Title |
Hydroxymethylation at Gene Regulatory Regions Directs Stem/Early Progenitor Cell Commitment during Erythropoiesis
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Published in |
Cell Reports, December 2013
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DOI | 10.1016/j.celrep.2013.11.044 |
Pubmed ID | |
Authors |
Jozef Madzo, Hui Liu, Alexis Rodriguez, Aparna Vasanthakumar, Sriram Sundaravel, Donne Bennett D. Caces, Timothy J. Looney, Li Zhang, Janet B. Lepore, Trisha Macrae, Robert Duszynski, Alan H. Shih, Chun-Xiao Song, Miao Yu, Yiting Yu, Robert Grossman, Brigitte Raumann, Amit Verma, Chuan He, Ross L. Levine, Don Lavelle, Bruce T. Lahn, Amittha Wickrema, Lucy A. Godley |
Abstract |
Hematopoietic stem cell differentiation involves the silencing of self-renewal genes and induction of a specific transcriptional program. Identification of multiple covalent cytosine modifications raises the question of how these derivatized bases influence stem cell commitment. Using a replicative primary human hematopoietic stem/progenitor cell differentiation system, we demonstrate dynamic changes of 5-hydroxymethylcytosine (5-hmC) during stem cell commitment and differentiation to the erythroid lineage. Genomic loci that maintain or gain 5-hmC density throughout erythroid differentiation contain binding sites for erythroid transcription factors and several factors not previously recognized as erythroid-specific factors. The functional importance of 5-hmC was demonstrated by impaired erythroid differentiation, with augmentation of myeloid potential, and disrupted 5-hmC patterning in leukemia patient-derived CD34+ stem/early progenitor cells with TET methylcytosine dioxygenase 2 (TET2) mutations. Thus, chemical conjugation and affinity purification of 5-hmC-enriched sequences followed by sequencing serve as resources for deciphering functional implications for gene expression during stem cell commitment and differentiation along a particular lineage. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 20% |
United Kingdom | 1 | 20% |
Unknown | 3 | 60% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 4 | 80% |
Science communicators (journalists, bloggers, editors) | 1 | 20% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 2 | 2% |
United Kingdom | 1 | <1% |
Czechia | 1 | <1% |
Unknown | 115 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 29 | 24% |
Student > Ph. D. Student | 28 | 24% |
Student > Master | 14 | 12% |
Student > Bachelor | 11 | 9% |
Student > Doctoral Student | 10 | 8% |
Other | 16 | 13% |
Unknown | 11 | 9% |
Readers by discipline | Count | As % |
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Agricultural and Biological Sciences | 55 | 46% |
Biochemistry, Genetics and Molecular Biology | 24 | 20% |
Medicine and Dentistry | 12 | 10% |
Chemistry | 4 | 3% |
Immunology and Microbiology | 3 | 3% |
Other | 9 | 8% |
Unknown | 12 | 10% |