PHD Finger - Function of The PHD Finger

Function of The PHD Finger

Recently the PHD fingers of some proteins, including ING2, YNG1 and NURF, have been reported to bind to histone H3 tri-methylated on lysine 4 (H3K4me3), while other PHD fingers have tested negative in such assays. Interestingly, a protein called SMCX (or JARID1C) has a PHD finger, which has been reported to bind histone H3 tri-methylated lysine 9 (H3K9me3). Based on these recent publications, binding to tri-methylated lysines on histones may therefore be a property widespread among PHD fingers. Domains that bind to modified histones, are called epigenetic readers as they specifically recognize the modified version of the residue and binds to it. The modification H3K4me3 is associated with the transcription start site of active genes, while H3K9me3 is associated with inactive genes. The modifications of the histone lysines are dynamic, as there are methylases that add methyl groups to the lysines, and there are demethylases that remove methyl groups. The SMCX protein is actually a histone H3 lysine 4 demethylase, which means it is an enzyme that can remove the methyl groups of lysine 4 on histone 3 (making it H3K4me2 or H3K4me1). One can only speculate if the H3K9me3-binding of SMCX PHD domain provides a crosstalk between trimethylation of H3K9 and the demethylation of H3K4me3. Such crosstalks have been suggested earlier with other domains involved in chromatin regulation, and may provide a strictly coordinated regulation.

Another example is the PHD finger of the BHC80/PHF21A protein, which is a component of the LSD1 complex. In this complex, LSD1 specifically demethylates H3K4me2 to H3K4me0, and BHC80 binds H3K4me0 through its PHD finger to stabilize the complex at its target promoters, presumably to prevent further re-methylation. This is the first example of a PHD finger recognizing lysine methyl-zero status.