H3.3S31 phosphorylation: linking transcription elongation to stimulation responses

摘要

Phosphorylation of histone proteins is involved in multiple cellularfunctions such as mitosis, DNA damage response, and transcriptionalregulation. For example, phosphorylation of H3.3 Ser31(H3.3S31ph) is known as a mitotic epigenetic modification.1 In arecent paper published on Nature, Armache et al. show thatH3.3S31ph has an unexpected function in stimulation-inducedtranscription through crosstalk with H3K36me3, an epigeneticmark for transcription elongation.2 In eukaryotic cells, DNA iswrapped around histone octamers, which contain two copies ofeach of the core histones H2A, H2B, H3, and H4. Most histones,also known as canonical histones, are synthesized and depositedonto chromatin only during S phase when DNA is beingreplicated. There are also other histones, known as histonevariants, that are expressed and synthesized in a cell cycleindependentmanner. Incorporation of histone variants intonucleosomes provides a means to regulate the chromatinarchitecture in addition to other epigenetic mechanisms. Histonevariants differ from canonical histones in just a few amino acids orlarge fractions of polypeptides. One of the histone variants, H3.3,has only four- or five-amino acid residue difference from canonicalH3, namely H3.1 and H3.2, respectively. Three amino acids arelocated in the histone core domain important for binding to H3.3-specific histone chaperones. The only different residue at the Nterminusof the protein is at position 31, which is an Alanine inH3.1 and H3.2 but replaced by highly conserved Serine in H3.3.Phosphorylation of H3.3S31 was first reported 15 years ago,1however, the function of this modification remains largelyunknown.