Epigenomic states contribute to coordinated allelic transcriptional bursting in iPSC reprogramming.

IF 3.3 2区 生物学 Q1 BIOLOGY
Life Science Alliance Pub Date : 2024-02-06 Print Date: 2024-04-01 DOI:10.26508/lsa.202302337
Parichitran Ayyamperumal, Hemant Chandru Naik, Amlan Jyoti Naskar, Lakshmi Sowjanya Bammidi, Srimonta Gayen
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引用次数: 0

Abstract

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.

表观基因组状态有助于 iPSC 重编程过程中等位基因转录突变的协调。
一个基因的两个等位基因可以独立转录,也可以协调转录,这可能导致时间表达异质性,对细胞命运产生不同的潜在影响。在这里,我们分析了 MEF 重编程为诱导多能干细胞过程中全基因组等位基因转录突变动力学。我们发现,等位基因突变的协调程度因基因而异,许多重编程相关基因的等位基因以高度协调的方式突变。值得注意的是,我们发现高度协调基因的两个等位基因的染色质可及性相似,这与半协调或独立基因不同,表明等位基因猝发的协调程度与等位基因染色质可及性有关。与此相一致,我们发现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。我们发现,高度协调的基因富含染色质可及性调节因子,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高度富集于高度协调的基因中。我们的研究表明,在诱导多能干细胞重编程过程中,表观基因组状态有助于协调等位基因突变,从而对基因表达进行微调。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Life Science Alliance
Life Science Alliance Agricultural and Biological Sciences-Plant Science
CiteScore
5.80
自引率
2.30%
发文量
241
审稿时长
10 weeks
期刊介绍: Life Science Alliance is a global, open-access, editorially independent, and peer-reviewed journal launched by an alliance of EMBO Press, Rockefeller University Press, and Cold Spring Harbor Laboratory Press. Life Science Alliance is committed to rapid, fair, and transparent publication of valuable research from across all areas in the life sciences.
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