KMT2A modulates the epigenetic landscape of rDNA by facilitating the recruitment of histone lysine acetyltransferase PCAF to the rDNA locus.

Histone acetylation, a commonly observed modification linked to the activation of numerous genes, plays a pivotal role in the dynamics of RNA Polymerase II. The specific contribution of histone acetylation to the transcriptional activation of RNA Polymerase I (RNA Pol I) remains less understood. In a recent study, researchers have uncovered that KMT2A interacts with ribosomal DNA (rDNA) loci.

Intriguingly, the absence of KMT2A does not influence the levels of H3K4me3 on rDNA. However, when KMT2A is absent, there is a marked reduction in H3 acetylation levels, with a particularly significant decrease in H3K9 acetylation. To identify the histone lysine acetyltransferases (KATs) that work in tandem with KMT2A to promote rDNA transcription, the researchers examined the occupancy and associated histone acetylation marks of several KATs on the rDNA locus.

They found that PCAF, a key KAT, is crucial for the KMT2A-mediated transcriptional activation of rDNA. When KMT2A levels are reduced, the levels of PCAF on rDNA also decrease, indicating that KMT2A acts as a co-activator in the recruitment of KATs to rDNA loci. Furthermore, the depletion of KMT2A disrupts the pre-initiation complex from the rDNA 47S promoter, leading to a stalled RNA Pol I complex at the spacer promoter.

This research sheds light on the unique and non-redundant function of KMT2A in regulating RNA Pol I transcription.