AI Article Synopsis
- Researchers developed a method using restriction enzymes and next-generation sequencing to identify accessible DNA elements, focusing on myeloid differentiation in human CD34+ cells.
- The study found that the accessibility of certain cis-regulatory elements could predict transcription factor binding and was linked to specific histone modifications.
- As cells differentiated, DNA accessibility decreased, correlating with fewer expressed genes and reduced regulatory potential, suggesting that chromatin structure becomes more closed and selective during differentiation.
Article 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.
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| http://dx.doi.org/10.1016/j.devcel.2009.02.002 | DOI Listing |
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