H3R42me2a is a histone modification with positive transcriptional effects

Abstract

Histone posttranslational modification leads to downstream effects indirectly by allowing or preventing docking of effector molecules, or directly by changing the intrinsic biophysical properties of local chromatin. To date, little has been done to study posttranslational modifications that lie outside of the unstructured tail domains of histones. Core residues, and in particular arginines in H3 and H4, mediate key interactions between the histone octamer and DNA in forming the nucleosomal particle. Using mass spectrometry, we find that one of these core residues, arginine 42 of histone H3 (H3R42), is dimethylated in mammalian cells by the methyltransferases coactivator arginine methyltransferase 1 (CARM1) and protein arginine methyltransferase 6 (PRMT6) in vitro and in vivo, and we demonstrate that methylation of H3R42 stimulates transcription in vitro from chromatinized templates. Thus, H3R42 is a new, "nontail" histone methylation site with positive effects on transcription. We propose that methylation of basic histone residues at the DNA interface may disrupt histone:DNA interactions, with effects on downstream processes, notably transcription.

Histone Core Phosphorylation Regulates DNA Accessibility

“…1A), potentially disrupting DNA-histone interactions. These observations, combined with previous results that H3K56ac and H3R42 trimethylation increase DNA unwrapping (26,37), suggest that H3Y41ph and H3T45ph may function to directly increase nucleosome unwrapping.…”

Mycobacteria modulate host epigenetic machinery by Rv1988 methylation of a non-tail arginine of histone H3

“…Both in in vitro reporter gene assay and in vivo infection experiments, we observed, repression owing to histone H3-arginine dimethylation by Rv1988. The difference in the results could be related to the use of synthetic chromatin in vitro transcription assay 34 versus the in vitro reporter gene assay and in vivo infection studies (this study). It is also possible that the difference was owing to symmetric versus asymmetric arginine dimethylation that is known to have opposite effects on transcription 36,37 .…”

“…A recent study showed by in vitro synthetic chromatin experiments that H3R42me 2, in presence of p53 and p300, acts to positively influence transcription 34 . On the other hand, in yeast, where a lysine is present instead of arginine at 42nd position, H3K42me 2 causes gene repression 33 .…”

“…Both in vitro histone H3 methylation assay and in vivo ChIP analysis on infected host macrophages (sequential double ChIP with H3 and dimethyl arginine antibodies, as well as a ChIP with H3R42me 2 antibody) confirmed that Rv1988 dimethylates histone H3 at R42. The interaction of Rv1988 with the host epigenetic circuitry through the non-tail core histone H3-arginine methylation (H3R42) is noteworthy because H3R42 is present at the critically important entry/exit point of DNA in the nucleosome that has the potential to change nucleosomal dynamics and affect transcription 33,34 . T W T W T W T W T W T W T W T NOXA1 CDC42BPB ncRNA NOX1 NOX4 NOS2 TNAIP2 TRAF3 NOXA1 CDC42BPB ncRNA NOX1 NOX4 NOS2 TNFAIP2 TRAF3 NOXA1 CDC42BPB ncRNA NOX1 NOX4 NOS2 TNFAIP2 The more important point to note here is the preference of Rv1988 for a non-tail core histone H3-arginine H3R42.…”

Protein Arginine Methyltransferase 6 (Prmt6) Is Essential for Early Zebrafish Development through the Direct Suppression of gadd45αa Stress Sensor Gene

“…Interestingly, there were 858 down-regulated genes in the prmt6 severe morphant that included zygotic genes and demonstrated the failure of zygotic genome activation. Therefore, whether Prmt6 directly contributes to zygotic genome activation through generating active modifications, such as H4R3me2a and H3R42me2a (14,18), deserves to be investigated. Additional ChIP-sequencing studies are required to determine whether the misregulated genes (see supplemental Table 1A) are directly regulated by Prmt6.…”