KMT2A modulates the epigenetic landscape of rDNA by facilitating the recruitment of histone lysine acetyltransferase PCAF to the rDNA locus.
- 1Centre for DNA Fingerprinting and Diagnostics (CDFD)
Abstract
Histone acetylation is often associated with transcriptional activation across a wide range of genes, playing a key role in RNA Polymerase II dynamics. However, its specific role in transcriptional activation of RNA Polymerase I (RNA Pol I) remains unclear. In this study, we demonstrate that KMT2A associates with ribosomal DNA (rDNA) loci. Notably, the loss of KMT2A in our inducible KO cell line does not affect the levels of H3K4me3 on rDNA. We support these observations with analyses of ChIP-seq data from mouse embryonic stem cells. While H3K4 methylation remains unchanged, the absence of KMT2A causes a significant decrease in H3 acetylation levels on rDNA, especially in H3K9 acetylation levels. To identify the histone lysine acetyl transferases (KATs) that cooperate with KMT2A in promoting rDNA transcription, we examined the occupancy of multiple KATs and their associated histone acetylation marks on the rDNA locus. Our analyses identify PCAF (p300/CBP associated factor) as the KAT that contributes to KMT2A-mediated transcriptional activation of rDNA. Depletion of KMT2A reduces the levels of PCAF on rDNA, suggesting that KMT2A plays the role of a co-activator of RNA Pol I in the recruitment of KATs on the rDNA loci. Finally, the depletion of KMT2A leads to the disruption of the pre-initiation complex from the rDNA 47S promoter, resulting in a stalled RNA Pol I complex at the spacer promoter. Our findings elucidate the non-redundant, distinct function of KMT2A in the regulation of RNA Pol I transcription.
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BibTeX
@misc{lone2026kmt2a,
title = {{KMT2A modulates the epigenetic landscape of rDNA by facilitating the recruitment of histone lysine acetyltransferase PCAF to the rDNA locus.}},
author = {K. A. Lone and A. Choudhary and A. K. Mahato and S. Tyagi},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.02.747590},
url = {https://www.biorxiv.org/content/10.64898/2026.09.02.747590v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - KMT2A modulates the epigenetic landscape of rDNA by facilitating the recruitment of histone lysine acetyltransferase PCAF to the rDNA locus.
AU - K. A. Lone
AU - A. Choudhary
AU - A. K. Mahato
AU - S. Tyagi
PY - 2026
DA - 2026/09/02
PB - bioRxiv
DO - 10.64898/2026.09.02.747590
UR - https://www.biorxiv.org/content/10.64898/2026.09.02.747590v1
AB - Histone acetylation is often associated with transcriptional activation across a wide range of genes, playing a key role in RNA Polymerase II dynamics. However, its specific role in transcriptional activation of RNA Polymerase I (RNA Pol I) remains unclear. In this study, we demonstrate that KMT2A associates with ribosomal DNA (rDNA) loci. Notably, the loss of KMT2A in our inducible KO cell line does not affect the levels of H3K4me3 on rDNA. We support these observations with analyses of ChIP-seq data from mouse embryonic stem cells. While H3K4 methylation remains unchanged, the absence of KMT2A causes a significant decrease in H3 acetylation levels on rDNA, especially in H3K9 acetylation levels. To identify the histone lysine acetyl transferases (KATs) that cooperate with KMT2A in promoting rDNA transcription, we examined the occupancy of multiple KATs and their associated histone acetylation marks on the rDNA locus. Our analyses identify PCAF (p300/CBP associated factor) as the KAT that contributes to KMT2A-mediated transcriptional activation of rDNA. Depletion of KMT2A reduces the levels of PCAF on rDNA, suggesting that KMT2A plays the role of a co-activator of RNA Pol I in the recruitment of KATs on the rDNA loci. Finally, the depletion of KMT2A leads to the disruption of the pre-initiation complex from the rDNA 47S promoter, resulting in a stalled RNA Pol I complex at the spacer promoter. Our findings elucidate the non-redundant, distinct function of KMT2A in the regulation of RNA Pol I transcription.
ER -