Chromatin state dynamics during blood formation

By D. Lara-Astiaso, A. Weiner, Erika Lorenzo-Vivas, I. Zaretsky, Diego Jaitin, Eyal David, Hadas Keren-Shaul, A. Mildner, D. Winter, Steffen Jung and 2 more. Science, 2014

711 citations recorded by the source corpus.

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 A chromatin precipitation technique identifies changes during the differentiation of blood cells. 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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/fb59aebb3f31292489c4f3888ca83cbd94ef926c

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In Cancer Research

1. Aviv Regev
2. M. Schwartz
3. Cole Trapnell
4. Jay Shendure
5. Jason D. Buenrostro

In Molecular Biology

1. Cole Trapnell
2. Caleb A. Lareau
3. Aviv Regev
4. Amos Tanay
5. Jay Shendure
6. Jiarui Ding
7. Ido Amit
8. Eyal David

Citations in the corpus

• Microglia development follows a stepwise program to regulate brain homeostasis (2016, methodology): “S3A), suggesting that chromatin changes precede changes in RNA (47).”
• Tissue-Resident Macrophage Enhancer Landscapes Are Shaped by the Local Microenvironment (2014, methodology): “Finally, we identified open chromatin regions through ATAC-seq (Buenrostro et al., 2013; Lara-Astiaso et al., 2014).”
• Chromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin (2020, background): “Prior studies comparing profiles of purified populations at distinct differentiation states have observed that changes in histone modifications and binding of lineage associated transcription factors (TFs) may precede and foreshadow changes in gene expression creating poised or primed chromatin stat”