Hydroxymethylation at gene regulatory regions directs stem/early progenitor cell commitment during erythropoiesis Journal Article

   

Authors:	Madzo, J.; Liu, H.; Rodriguez, A.; Vasanthakumar, A.; Sundaravel, S.; Caces, D.; Looney, T.; Zhang, L.; Lepore, J.; Macrae, T.; Duszynski, R.; Shih, A.; Song, C. X.; Yu, M.; Yu, Y.; Grossman, R.; Raumann, B.; Verma, A.; He, C.; Levine, R.; Lavelle, D.; Lahn, B.; Wickrema, A.; Godley, L.
Article Title:	Hydroxymethylation at gene regulatory regions directs stem/early progenitor cell commitment during erythropoiesis
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. © 2014 The Authors.
Journal Title:	Cell Reports
Volume:	6
Issue:	1
ISSN:	2211-1247
Publisher:	Cell Press
Date Published:	2014-01-16
Start Page:	231
End Page:	244
Language:	English
DOI:	10.1016/j.celrep.2013.11.044
PROVIDER:	scopus
PMCID:	PMC3976649
PUBMED:	24373966
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84892540146&partnerID=40&md5=74df393ebb85864c103da1c94ed2ef42
Notes:	Export Date: 3 March 2014 -- Source: Scopus

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