ArticleMolecular cell2023
Gene silencing dynamics are modulated by transiently active regulatory elements.
Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- DNA methylation profiles aid to identify putative genome activation histories along lymphomagenesis.NAR genomics and bioinformatics · 2026Article
- Enhancer-dependent gene regulation in space, time, and malignancies.International journal of cancer · 2026Review
- Temporal constraints on enhancer usage shape the regulation of limb gene transcription.Nature communications · 2026Article
- Engineering the Link: From Genome Interaction Maps to Functional Insight.Advanced biology · 2025Review
- CTCF depletion decouples enhancer-mediated gene activation from chromatin hub formation.Nature structural & molecular biology · 2025Article
- CTCF is selectively required for maintaining chromatin accessibility and gene expression in human erythropoiesis.Genome biology · 2025Article
- R-loops and small RNA regulatory interactions: mechanisms and clinical perspectives.Frontiers in cell and developmental biology · 2025Review
- The hidden world of transient enhancers.Nature reviews. Genetics · 2024Article
- Pioneer and PRDM transcription factors coordinate bivalent epigenetic states to safeguard cell fate.Molecular cell · 2024Article
- Emerging insights into enhancer biology and function.Transcription · 2023Review
- Carm1-arginine methylation of the transcription factor C/EBPα regulates transdifferentiation velocity.eLife · 2023Article
- The winding road toward transcriptional repression.Molecular cell · 2023Article
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Transcriptional enhancers have been extensively characterized, but cis-regulatory elements involved in acute gene repression have received less attention. Transcription factor GATA1 promotes erythroid differentiation by activating and repressing distinct gene sets. Here, we study the mechanism by which GATA1 silences the proliferative gene Kit during murine erythroid cell maturation and define stages from initial loss of activation to heterochromatinization. We find that GATA1 inactivates a potent upstream enhancer but concomitantly creates a discrete intronic regulatory region marked by H3K27ac, short noncoding RNAs, and de novo chromatin looping. This enhancer-like element forms transiently and serves to delay Kit silencing. The element is ultimately erased via the FOG1/NuRD deacetylase complex, as revealed by the study of a disease-associated GATA1 variant. Hence, regulatory sites can be self-limiting by dynamic co-factor usage. Genome-wide analyses across cell types and species uncover transiently active elements at numerous genes during repression, suggesting that modulation of silencing kinetics is widespread.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.