Histone H3K4me1 and H3K27ac play roles in nucleosome eviction and eRNA transcription, respectively, at enhancers
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Abstract
Histone H3K4me1 and H3K27ac are enhancer‐specific modifications and are required for enhancers to activate transcription of target genes. However, the reciprocal effects of these histone modifications on each other and their roles in enhancers are not clear. Here to comparatively analyze the role of these modifications, we inhibited H3K4me1 and H3K27ac by deleting the SET domains of histone methyltransferases MLL3 and MLL4 and the HAT domain of histone acetyltransferase p300, respectively, in erythroid K562 cells. The loss of H3K4me1 reduced H3K27ac at the β‐globin enhancer LCR HSs, but H3K27ac reduction did not affect H3K4me1. This unequal relationship between two modifications was revealed in putative enhancers by genome‐wide analysis using ChIP‐seq. Histone H3 eviction at putative enhancers was weakened by the loss of H3K4me1 but not by the loss of H3K27ac. Chromatin remodeling complexes were recruited into the β‐globin LCR HSs in a H3K4me1‐dependent manner. In contrast, H3K27ac was required for enhancer RNA (eRNA) transcription, and H3K4me1 was not enough for it. Forced H3K27ac‐induced eRNA transcription without affecting H3K4me1 at the β‐globin LCR HSs. These results indicate that H3K4me1 and H3K27ac affect each other in different ways and play more direct roles in nucleosome eviction and eRNA transcription, respectively, at enhancers.
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Without HNF4A, nucleosome positioning is disrupted.
“This suggests that without HNF4A, the nucleosome positioning is disrupted, which may be a result of the fact that the loss of H3K4me1 reduces H3 eviction from the region34.”
From HNF4A guides the MLL4 complex to establish and maintain H3K4me1 at gene regulatory elements (2024) · cites this paper as [34]
The genome-wide analysis reports that loss of H3K4me1 reduced histone H3 depletion at putative enhancers, supporting the cited sentence’s proposed mechanism. But the paper examines MLL3/4-altered K562 cells, not loss of HNF4A, and does not establish that nucleosome positioning is disrupted without HNF4A. No page number is available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredH3K27ac at gene regulatory regions is dependent on the presence of H3K4me1, indicating H3K4me1 defines the future active enhancer.
“The active histone modification H3K27ac at gene regulatory regions is dependent on the presence of H3K4me1, indicating H3K4me1 defines the future active enhancer30,34.”
From HNF4A guides the MLL4 complex to establish and maintain H3K4me1 at gene regulatory elements (2024) · cites this paper as [34]
The genome-wide analysis section states that H3K27ac depends on H3K4me1 at putative enhancers. The eRNA transcription section also describes enhancers as prepared by H3K4me1. Neither passage establishes that H3K4me1 identifies which enhancers will become active in the future. (LLM, conf=0.84)
Experimental — accuracy not yet measuredLoss of H3K4me1 reduces H3 eviction from the region.
“which may be a result of the fact that the loss of H3K4me1 reduces H3 eviction from the region34.”
From HNF4A guides the MLL4 complex to establish and maintain H3K4me1 at gene regulatory elements (2024) · cites this paper as [34]
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- Authors
- Kang, Y., Kim, Y. W., Kang, J., & Kim, A.
- Affiliations
- Pusan National University (KR)
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2021-07-26
- Volume
- 35
- Issue
- 8
- Pages
- e21781-e21781
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W3186647381
- Cited by
- 93
- References
- 61
- Citations by year
- 2026: 12 · 2025: 24 · 2024: 29 · 2023: 13 · 2022: 13 · 2021: 2
- FWCI
- 4.47
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- The FASEB Journal (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation of Korea
- Ministry of Science, ICT and Future Planning (NRF‐2014R1A2A1A11051702)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- H3K4me1, H3K27ac, enhancers, nucleosome eviction, histone modifications, MLL3, KMT2D, P300, histone methyltransferase, histone acetyltransferase, beta-globin locus control region, chromatin remodeling complexes, erythroid cells, K562 cells
- MeSH terms
- Chromatin, Enhancer Elements, Genetic, Histones, Humans, Methylation, Nucleosomes, RNA, Transcriptional Activation, K562 Cells, Histone Code
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