Immunogenetics. Chromatin state dynamics during blood formation.
basic_science · Level V
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- Record sourced from PubMed, PMID 25103404.
- Also identified by DOI 10.1126/science.1256271 and PMC identifier 4412442.
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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.
Medical subject headings
- Chromatin
- Enhancer Elements, Genetic
- Gene Expression Regulation
- Hematopoiesis
- Hematopoietic Stem Cells
- Transcription Factors