https://ror.org/04dese585 Chromatin, RNA and Genome (CRG) Laboratory, Department of Developmental Biology and Genetics, Indian Institute of Science, Bangalore, India.
https://ror.org/04dese585 Chromatin, RNA and Genome (CRG) Laboratory, Department of Developmental Biology and Genetics, Indian Institute of Science, Bangalore, India
Life Sci Alliance. 2024 Feb 6;7(4). doi: 10.26508/lsa.202302337. Print 2024 Apr.
Two alleles of a gene can be transcribed independently or coordinatedly, which can lead to temporal expression heterogeneity with potentially distinct impacts on cell fate. Here, we profiled genome-wide allelic transcriptional burst kinetics during the reprogramming of MEF to induced pluripotent stem cells. We show that the degree of coordination of allelic bursting differs among genes, and alleles of many reprogramming-related genes burst in a highly coordinated fashion. Notably, we show that the chromatin accessibility of the two alleles of highly coordinated genes is similar, unlike the semi-coordinated or independent genes, suggesting the degree of coordination of allelic bursting is linked to allelic chromatin accessibility. Consistently, we show that many transcription factors have differential binding affinity between alleles of semi-coordinated or independent genes. We show that highly coordinated genes are enriched with chromatin accessibility regulators such as H3K4me3, H3K4me1, H3K36me3, H3K27ac, histone variant H3.3, and BRD4. Finally, we demonstrate that enhancer elements are highly enriched in highly coordinated genes. Our study demonstrates that epigenomic states contribute to coordinated allelic bursting to fine-tune gene expression during induced pluripotent stem cell reprogramming.
两个基因的等位基因可以独立或协调转录，这可能导致细胞命运具有潜在不同影响的时间表达异质性。在这里，我们在 MEF 重编程为诱导多能干细胞的过程中，对全基因组等位基因转录爆发动力学进行了分析。我们表明，等位基因爆发的协调程度在基因之间存在差异，许多与重编程相关的基因的等位基因以高度协调的方式爆发。值得注意的是，我们表明，高度协调基因的两个等位基因的染色质可及性相似，与半协调或独立基因不同，这表明等位基因爆发的协调程度与等位基因染色质可及性有关。一致地，我们表明，许多转录因子在半协调或独立基因的等位基因之间具有不同的结合亲和力。我们表明，高度协调的基因富含染色质可及性调节剂，如 H3K4me3、H3K4me1、H3K36me3、H3K27ac、组蛋白变体 H3.3 和 BRD4。最后，我们证明增强子元件在高度协调的基因中高度富集。我们的研究表明，表观基因组状态有助于协调等位基因爆发，以在诱导多能干细胞重编程过程中精细调节基因表达。
