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Chromatin state dynamics during blood formation

Science  22 Aug 2014:
Vol. 345, Issue 6199, pp. 943-949
DOI: 10.1126/science.1256271

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Opening and closing blood enhancers

As cells develop and differentiate into different types, the shape and accessibility of their DNA can change. Lara-Astiaso et al. studied this phenomenon in blood. They developed a technique that examines a relatively small number of cells to identify the changes that affect DNA during blood development. They found that the DNA of noncoding regions, called enhancers, is set in an open position when cells are undifferentiated and able to take on a variety of roles and gradually closes as cells mature into their final forms.

Science, this issue p. 943

Abstract

Chromatin modifications are crucial for development, yet little is known about their dynamics during differentiation. Hematopoiesis provides a well-defined model to study chromatin state dynamics; however, technical limitations impede profiling of homogeneous differentiation intermediates. We developed a high-sensitivity indexing-first chromatin immunoprecipitation approach to profile the dynamics of four chromatin modifications across 16 stages of hematopoietic differentiation. We identify 48,415 enhancer regions and characterize their dynamics. We find that lineage commitment involves de novo establishment of 17,035 lineage-specific enhancers. These enhancer repertoire expansions foreshadow transcriptional programs in differentiated cells. Combining our enhancer catalog with gene expression profiles, we elucidate the transcription factor network controlling chromatin dynamics and lineage specification in hematopoiesis. Together, our results provide a comprehensive model of chromatin dynamics during development.

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