PHD finger protein 20 (PHF20) binds dimethyl lysine residues via its Tudor domain []. It is a component of the MLL1, MOF histone acetyltransferase []and NSL protein complexes [].The NSL complex is involved in acetylation of nucleosomal histone H4 on several lysine residues and therefore may be involved in the regulation of transcription. The complex is composed of at least MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1 [].
Host cell factor 1 (HCFC1) is associated with the activation and repression of gene expression. It is brought to specific promoters by association with DNA-sequence-specific transcription factors such as Sp1, GABP, YY1, Ronin/THAP11, and E2F1 and E2F4 []. HCFC1 recruits and is a part of several different complexes, including the SET1 histone methyltransferase complex (transcription activation), the SIN3 histone deacetylase complex (transcription repression) [], the THAP1/THAP3-HCFC1-OGT complex (required for the regulation of the transcriptional activity of RRM1) [], and the NSL complex (acetylation of nucleosomal histone H4) []. This entry includes mammalian HCFC1 and the Drosophila homologue, dHCF. They undergo a process of proteolytic maturation to produce a heterodimeric complex of HCF-N and HCF-C subunits, by different enzymes, O-GlcNAc transferase and taspase1, respectively [, ]. They share a Kelch domain, regions biased for basic (Basic) or acidic (Acidic) amino acids, fibronectin type 3 repeats, and a nuclear localization signal [].During human herpes simplex virus infection, HCFC1 forms a multiprotein-DNA complex enabling transcription of the virus's early genes []. It is also a co-activator of EGR2/Krox20 []and the GA-binding protein GABP2 [], and represses ZBTB17/Miz-1 [].
In animals, histone-lysine N-methyltransferase SETD1A () is a histone methyltransferase that produces mono-, di-, and trimethylated histone H3 at 'Lys-4. However, if 'Lys-9' residue is already methylated, 'Lys-4' will not be. The 'Lys-4' methylation is a tag for epigenetic transcriptional activation [, ]. The SET1 complex contains either SETD1A or SETD1B.The SET1 complex is a methyltransferase that that produces trimethylated histone H3 at Lys(4). It is composed of at least the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30 []. In yeast there is only one SET1 complex, but in mammals there are additional H3K4 methylases [].
Histone-lysine N-methyltransferase SETD1B () is a histone methyltransferase that produces trimethylated histone H3 at 'Lys-4'. However, if 'Lys-9' residue is already methylated, 'Lys-4' will not be. The 'Lys-4' methylation is a tag for epigenetic transcriptional activation []. The SET1 complex contains either SETD1A or SETD1B.The SET1 complex is a methyltransferase that that produces trimethylated histone H3 at Lys(4). It is composed of at least the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30 []. In yeast there is only one SET1 complex, but in mammals there are additional H3K4 methylases [].
The UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase (OGT; ) is a heterotrimer of one 78kDa subunit and two 110kDa subunits. OGT catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in a protein. Substrate proteins include histone H2B, AKT1, EZH2, PFKL, KMT2E/MLL5, MAPT/TAU and HCFC1. The consequences of this form of glycosylation are diverse, including insulin resistance in muscle and adipocyte cells (brought about by inhibiting the 'Thr-308' phosphorylation of AKT1) []; regulation of glycolysis by inhibiting PFKL activity []; in the cell cycle O-glycosylation stabilizes ARNTL/BMAL1 and CLOCK, preventing their ubiquitination and subsequent degradation []; glycosylation of HCFC1 and interaction with TET proteins promotes binding of the SET1/COMPASS methyltransferase SETD1A to chromatin []; and H2B GlcNAcylation is a histone modification that facilitates H2BK120 monoubiquitination []. It is a component of several complexes, including MLL5-L, NSL []and THAP1/THAP3-HCFC1-OGT [].This entry represents the 110kDa subunit which has thirteen tetratricopeptide (TPR) repeats that are required for substrate binding and oligomerization [].The NSL complex is involved in acetylation of nucleosomal histone H4 on several lysine residues and therefore may be involved in the regulation of transcription. The complex is composed of at least MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1 [].
This entry includes Sdc1 from yeasts, and its homologues, Dpy-30, from animals. Protein dpy-30 homologue (DPY30) is a component of the MLL1/MLL complex which trimethylates histone H3 at 'Lys-4' as a specific tag for epigenetic transcriptional activation []. DPY30 is also a component in MLL2/3 and MLL4/WBP7 methyltransferase-containing complexes [, ]and the SET1 complex []. DPY30 is found in the nucleus and the trans-Golgi network where it interacts with ARFGEF1 implying a role in endosomal trafficking []. This entry also includes C. elegans dpy-30, which is an essential component of the C. elegans dosage compensation machinery that reduces X chromosome transcript levels in hermaphrodites (XX) [].The SET1 complex is a methyltransferase that that produces trimethylated histone H3 at Lys(4). It is composed of at least the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30 []. In yeast there is only one SET1 complex, but in mammals there are additional H3K4 methylases [].
This entry includes Host cell factor 1 (HCF1) and Host cell factor 2 (HCF2) from humans. They contain an N-terminal kelch domain and a C-terminal FnIII domain. However, HCF2 is smaller than HCF-1, lacking the complete central region including the HCF1 specific repeats and as a result is not subject to proteolytic processing []. This entry also includes their Drosophila melanogaster homologue, dHCF, which is involved in both activation and repression of transcription during fly development []. Host cell factor homologue hcf-1 from C. elegans controls the cell cycle through mitotic histone phosphorylation modulation and negatively regulates responses to environmental stresses [].HCF1 is associated with the activation and repression of gene expression. It is brought to specific promoters by association with DNA-sequence-specific transcription factors such as Sp1, GABP, YY1, Ronin/THAP11, and E2F1 and E2F4 []. HCFC1 recruits and is a part of several different complexes, including the SET1 histone methyltransferase complex (transcription activation), the SIN3 histone deacetylase complex (transcription repression) [], the THAP1/THAP3-HCFC1-OGT complex (required for the regulation of the transcriptional activity of RRM1) [], and the NSL complex (acetylation of nucleosomal histone H4) [].HCF2 is involved in activation of differentiation and morphogenesis gene expression programs, and in parallel in inhibition of cellular growth and metabolism [].
The COMPASS complex (complex proteins associated with Set1) is conserved in yeasts and in other eukaryotes up to humans. This entry represents Set1 and its homologues. Set1 is a methyltransferase and the catalytic component of the COMPASS that produces trimethylated histone H3 at Lys(4). The yeast COMPASS (Set1C) complex specifically mono-, di- and trimethylates histone H3 to form H3K4me1/2/3, which subsequently plays a role in telomere length maintenance and transcription elongation regulation [, , ]. In yeasts, the Set1C complex consists of Set1(2), Bre2(2), Spp1(2), Sdc1(1), Shg1(1), Swd1(1), Swd2(1), and Swd3(1) [, , , ].In animals, SETD1A/B are histone methyltransferases that produce mono-, di-, and trimethylated histone H3 at 'Lys-4. However, if 'Lys-9' residue is already methylated, 'Lys-4' will not be. The 'Lys-4' methylation is a tag for epigenetic transcriptional activation [, ]. The animal COMPASS complex is composed of at least the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30 []. ATXR7, the Arabidopsis homologue to Set1, is required for the expression of the flowering repressors FLC and MADS-box genes of the MAF family [, ]. ATXR7 is also involved in the control of seed dormancy and germination [].
