长链非编码RNA分子（lncRNA）是哺乳动物转录组的重要组分，也是高等生物重要的遗传性调控因子。目前，虽有大量lncRNA被不断发现，但对其功能和机制的阐释仍相对滞后，尤其是缺乏功能性lncRNA筛选和研究的独特视角。本课题以造血红系发育过程中标志性的基因表达驱动事件"GATA switch"为切入点，系统性鉴定受红系关键转录因子GATA-1和GATA-2"转换"调节的lncRNA分子；在确定Lincred1为研究对象后，重点在造血干/祖细胞和基因敲除小鼠中考察Lincred1调节红系发育的生物学功能；同时通过研究Lincred1与多梳蛋白Pc2的相互作用、Pc2对GATA-1的SUMO化修饰作用、以及SUMO化修饰对"GATA switch"的影响，阐明Lincred1的作用机制。这不仅为功能特异性lncRNA的鉴定提供新的筛选策略，更为揭示和丰富lncRNA的作用机制提供新的依据。

A major fraction of the transcriptome of higher organisms comprised an extensive repertoire of long non-coding RNA (lncRNA) which are recognized as essential regulators in various cellular processes. Up to date, although numerous lncRNA has been identified, an existing challenge is to understand how the molecular functions of lncRNAs affect the phenotypes of the organisms. Limited by screening strategies and technological advances, the main problem in lncRNA study remains the identification of biologically functional lncRNAs. In this work, we started from an erythroid landmark event termed "GATA switch", which involves GATA-1-mediated displacement of GATA-2 from chromatin. Given that "GATA switch" often occurs at loci with critical functions, we aim to identify important lncRNAs that are under the control by this developmental control tools. As a result, we focused on the candidate Lincred1 to further analyze its regulatory roles during erythropoiesis in cell lines, primary cultured hematopoietic stem/progenitor cells and conditional transgenic mouse models. Since the SUMO E3 ligase Pc2 (polycomb protein 2), harboring an RNA binding domain, was shown to be associated with Lincred1 in our previous study, we will further confirm the interaction between Lincred1 and Pc2, assess their cooperativity in regulating GATA-1 sumoylation, thus evaluating their influence on GATA factors switching. By clarifying the function and molecular mechanism of Lincred1 in erythropoiesis, this strategy will be successfully used to identify lncRNAs that are relevant to the specific biological question. These results will also provide new insights into lncRNA study and gene regulatory networks in hematopoiesis.