Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Institute of Life Sciences, The Hebrew University, Jerusalem, Israel. School of Computer Science and Engineering, The Hebrew University, Jerusalem, Israel.
Science. 2014 Aug 22;345(6199):943-9. doi: 10.1126/science.1256271. Epub 2014 Aug 7.
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.
染色质修饰对于发育至关重要，但人们对其在分化过程中的动态变化知之甚少。造血提供了一个研究染色质状态动态变化的明确模型；然而，技术限制阻碍了对同质分化中间产物的分析。我们开发了一种高灵敏度的索引优先染色质免疫沉淀方法，来分析造血分化的 16 个阶段中四种染色质修饰的动态变化。我们鉴定了 48415 个增强子区域，并对其动态变化进行了描述。我们发现谱系特化涉及到 17035 个谱系特异性增强子的从头建立。这些增强子库的扩展预示着分化细胞中的转录程序。将我们的增强子目录与基因表达谱相结合，我们阐明了控制造血中染色质动力学和谱系特化的转录因子网络。总的来说，我们的研究结果提供了一个全面的发育过程中染色质动力学模型。
