Binding to RNA regulates Set1 function.

Area of Science:

• Molecular Biology
• Epigenetics
• RNA Biology

Background:

• The Set1 complex is a conserved histone methyltransferase responsible for H3K4 methylation.
• Histone methylation plays a critical role in gene regulation and chromatin structure.
• Understanding the regulatory mechanisms of Set1 complex is essential for deciphering gene expression control.

Purpose of the Study:

• To investigate the direct interaction between the Set1 complex and RNA.
• To elucidate the functional significance of RNA binding by Set1 complex in gene transcription.
• To explore the implications of Set1 complex-RNA interactions in cellular adaptive responses.

Main Methods:

• In vitro binding assays to demonstrate direct RNA binding.
• UV RNA crosslinking (CRAC) coupled with ChIP-seq to map Set1 and RNA polymerase II binding sites.
• Analysis of Set1 complex distribution along transcription units.

Main Results:

• The Set1 complex directly binds RNA through its double RNA recognition motifs (dRRM) and N-SET domain.
• Set1 complex binding to nascent transcripts is mediated by its dRRM.
• RNA binding influences Set1 complex distribution and H3K4me3 deposition during transcription.
• Set1 complex exhibits preferential binding to specific RNA classes, including SET1, Ty1 retrotransposons, transcription factor genes, and snRNAs.

Conclusions:

• RNA binding is an integral function of the Set1 complex, impacting its genomic distribution and epigenetic activity.
• Set1 complex's interaction with specific RNAs suggests a role in post-transcriptional regulation and adaptive cellular responses.
• The findings reveal a novel layer of gene regulation involving the interplay between histone methylation and RNA binding by the Set1 complex.