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NA-Seq: a discovery tool for the analysis of chromatin structure and dynamics during differentiation

Item Type:Article
Title:NA-Seq: a discovery tool for the analysis of chromatin structure and dynamics during differentiation
Creators Name:Gargiulo, G. and Levy, S. and Bucci, G. and Romanenghi, M. and Fornasari, L. and Beeson, K.Y. and Goldberg, S.M. and Cesaroni, M. and Ballarini, M. and Santoro, F. and Bezman, N. and Frige, G. and Gregory, P.D. and Holmes, M.C. and Strausberg, R.L. and Pelicci, P.G. and Urnov, F.D. and Minucci, S.
Abstract:It is well established that epigenetic modulation of genome accessibility in chromatin occurs during biological processes. Here we describe a method based on restriction enzymes and next-generation sequencing for identifying accessible DNA elements using a small amount of starting material, and use it to examine myeloid differentiation of primary human CD34+ cells. The accessibility of several classes of cis-regulatory elements was a predictive marker of in vivo DNA binding by transcription factors, and was associated with distinct patterns of histone posttranslational modifications. We also mapped large chromosomal domains with differential accessibility in progenitors and maturing cells. Accessibility became restricted during differentiation, correlating with a decreased number of expressed genes and loss of regulatory potential. Our data suggest that a permissive chromatin structure in multipotent cells is progressively and selectively closed during differentiation, and illustrate the use of our method for the identification of functional cis-regulatory elements.
Keywords:CD34 Antigens, Cell Differentiation, Chromatin, Cultured Cells, Developmental Gene Expression Regulation, DNA Restriction Enzymes, Genetic Epigenesis, Genome-Wide Association Study, Hematopoietic Stem Cells, Histones, Myelopoiesis, Transcription Factors
Source:Developmental Cell
Publisher:Cell Press / Elsevier
Page Range:466-481
Date:17 March 2009
Official Publication:https://doi.org/10.1016/j.devcel.2009.02.002
PubMed:View item in PubMed

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