NA-Seq: A Discovery Tool for the Analysis of Chromatin Structure and Dynamics during Differentiation

被引：45

作者：

Gargiulo, Gaetano ^{[1
]}

Levy, Samuel ^{[2
]}

Bucci, Gabriele ^{[1
]}

Romanenghi, Mauro ^{[1
]}

Fornasari, Lorenzo ^{[3
]}

Beeson, Karen Y. ^{[2
]}

Goldberg, Susanne M. ^{[2
]}

Cesaroni, Matteo ^{[1
]}

Ballarini, Marco ^{[3
]}

Santoro, Fabio ^{[3
]}

Bezman, Natalie ^{[4
]}

Frige, Gianmaria ^{[1
]}

Gregory, Philip D. ^{[4
]}

Holmes, Michael C. ^{[4
]}

Strausberg, Robert L. ^{[2
]}

Pelicci, Pier Giuseppe ^{[1
]}

Urnov, Fyodor D. ^{[4
]}

Minucci, Saverio ^{[1
,5
]}

机构：

[1] European Inst Oncol, IFOM Campus, Dept Expt Oncol, I-20141 Milan, Italy

[2] J Craig Venter Inst, Rockville, MD 20850 USA

[3] Genextra Grp, I-20121 Milan, Italy

[4] Sangamo BioSci, Richmond, CA 94804 USA

[5] Univ Milan, Dept Biomol Sci & Biotechnol, I-20133 Milan, Italy

来源：

DEVELOPMENTAL CELL | 2009年 / 16卷 / 03期

关键词：

HUMAN GENOME; HYPERSENSITIVE SITES; REGULATORY ELEMENTS; BINDING SITES; GENE; METHYLATION; PATTERNS; CELLS; IDENTIFICATION; ORGANIZATION;

D O I：

10.1016/j.devcel.2009.02.002

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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 post-translational 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.

引用

页码：466 / 481

页数：16

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