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Epigenomic states contribute to coordinated allelic transcriptional bursting in iPSC reprogramming

Ayyamperumal, P and Naik, HC and Naskar, AJ and Bammidi, LS and Gayen, S (2024) Epigenomic states contribute to coordinated allelic transcriptional bursting in iPSC reprogramming. In: Life Science Alliance, 7 (4).

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Official URL: https://doi.org/10.26508/lsa.202302337

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. © 2024 Ayyamperumal et al.

Item Type: Journal Article
Publication: Life Science Alliance
Publisher: Life Science Alliance, LLC
Additional Information: The copyright for this article belongs to the Authors.
Keywords: nuclear protein; transcription factor, allele; chromatin; epigenetics; genetics; induced pluripotent stem cell; metabolism, Alleles; Chromatin; Epigenomics; Induced Pluripotent Stem Cells; Nuclear Proteins; Transcription Factors
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited: 23 Apr 2024 07:32
Last Modified: 23 Apr 2024 07:32
URI: https://eprints.iisc.ac.in/id/eprint/84635

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