具有二价组蛋白标记的复合转座子在细胞命运调控中发挥RNA依赖性增强子的作用，这一成果由清华大学刘念研究团队经过不懈努力而取得。2025年8月6日，国际知名学术期刊《细胞》发表了这一成果。
该课题组研究人员报道复合转座子含有双价组蛋白标记，在不同的区域具有激活和抑制标记。全基因组CRISPR-Cas9筛选，在人类细胞中筛选了一个由古人类特异性复合转座子SVA（SINE[短穿插核元件]-VNTR[可变数目串联重复序列]-Alu）驱动的报告基因，发现了多种修饰二价组蛋白标记以调节SVA转录的基因。SVA转录本是SVA选择性接触和激活远程基因表达的顺式调控功能的关键。值得注意的是，一组二价SVAs在红细胞生成过程中被激活，以促进多个红细胞基因的表达，而敲低这些SVAs会导致红细胞生成缺陷。SVA的RNA依赖性顺式调节功能激活骨髓形成基因，并有助于衰老相关的骨髓偏向性造血。这些结果表明，复合转座子的顺式调控功能在发育和衰老过程中受到二价调控，从而控制细胞命运的转变。
据悉，离散的基因组单位可以重组成复合转座子，这些转座子作为单个单位进行转录和转座，但它们的调控和功能尚不完全清楚。
附：英文原文
Title: Composite transposons with bivalent histone marks function as RNA-dependent enhancers in cell fate regulation
Author: Ziqiang Zhou, Shicong Zhu, Yaqiang Hong, Guangpu Jin, Rui Ma, Fan Lin, Yiyang Zhang, Hsiang-Ying Lee, Nian Liu
Issue&Volume: 2025-08-06
Abstract: Discrete genomic units can recombine into composite transposons that transcribe and transpose as single units, but their regulation and function are not fully understood. We report that composite transposons harbor bivalent histone marks, with activating and repressive marks in distinct regions. Genome-wide CRISPR-Cas9 screening, using a reporter driven by the hominid-specific composite transposon SVA (SINE [short interspersed nuclear element]-VNTR [variable number of tandem repeats]-Alu) in human cells, identified diverse genes that modify bivalent histone marks to regulate SVA transcription. SVA transcripts are critical for SVA’s cis-regulatory function in selectively contacting and activating long-range gene expression. Remarkably, a subset of bivalent SVAs is activated during erythropoiesis to boost multiple erythroid gene expression, and knocking down these SVAs leads to deficient erythropoiesis. The RNA-dependent cis-regulatory function of SVA activates genes for myelopoiesis and can contribute to aging-associated myeloid-biased hematopoiesis. These results reveal that the cis-regulatory functions of composite transposons are bivalently regulated to control cell fate transitions in development and aging.
DOI: 10.1016/j.cell.2025.07.014
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00803-7