Karia Dimple, Gilbert Robert C G, Biasutto Antonio J, Porcher Catherine, Mancini Erika J
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Department of Biochemistry, University of Oxford, 3 S Parks Road, Oxford OX1 3QU, UK.
R Soc Open Sci. 2020 Jan 29;7(1):191048. doi: 10.1098/rsos.191048. eCollection 2020 Jan.
Chromatin remodelling and transcription factors play important roles in lineage commitment and development through control of gene expression. Activation of selected lineage-specific genes and repression of alternative lineage-affiliated genes result in tightly regulated cell differentiation transcriptional programmes. However, the complex functional and physical interplay between transcription factors and chromatin-modifying enzymes remains elusive. Recent evidence has implicated histone demethylases in normal haematopoietic differentiation as well as in malignant haematopoiesis. Here, we report an interaction between H3K4 demethylase JARID1A and the haematopoietic-specific master transcription proteins SCL and GATA1 in red blood cells. Specifically, we observe a direct physical contact between GATA1 and the second PHD domain of JARID1A. This interaction has potential implications for normal and malignant haematopoiesis.
染色质重塑和转录因子通过控制基因表达在谱系定向和发育过程中发挥重要作用。选定的谱系特异性基因的激活以及其他谱系相关基因的抑制导致细胞分化转录程序受到严格调控。然而，转录因子与染色质修饰酶之间复杂的功能和物理相互作用仍不清楚。最近的证据表明组蛋白去甲基化酶在正常造血分化以及恶性造血过程中发挥作用。在此，我们报道了红细胞中H3K4去甲基化酶JARID1A与造血特异性主转录蛋白SCL和GATA1之间的相互作用。具体而言，我们观察到GATA1与JARID1A的第二个PHD结构域之间存在直接的物理接触。这种相互作用对正常和恶性造血具有潜在影响。
