Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Genome Res. 2011 Oct;21(10):1650-8. doi: 10.1101/gr.121145.111. Epub 2011 Jul 27.
Enhancers of transcription activate transcription via binding of sequence-specific transcription factors to their target sites in chromatin. In this report, we identify GATA1-bound distal sites genome-wide and find a global reorganization of the nucleosomes at these potential enhancers during differentiation of hematopoietic stem cells (HSCs) to erythrocytes. We show that the catalytic subunit BRG1 of BAF complexes localizes to these distal sites during differentiation and generates a longer nucleosome linker region surrounding the GATA1 sites by shifting the flanking nucleosomes away. Intriguingly, we find that the nucleosome shifting specifically facilitates binding of TAL1 but not GATA1 and is linked to subsequent transcriptional regulation of target genes.
转录增强子通过序列特异性转录因子与其在染色质中的靶位点结合来激活转录。在本报告中，我们在全基因组范围内鉴定了 GATA1 结合的远端位点，并发现造血干细胞（HSCs）分化为红细胞过程中这些潜在增强子处的核小体发生了全局重排。我们表明，BAF 复合物的催化亚基 BRG1 在分化过程中定位于这些远端位点，并通过将侧翼核小体移开，在 GATA1 位点周围产生更长的核小体连接区。有趣的是，我们发现核小体的移位特异性地促进了 TAL1 的结合，但不促进 GATA1 的结合，并与靶基因随后的转录调控相关。
