MLL5, a histone modifying enzyme, regulates androgen receptor activity in prostate cancer cells by recruiting co-regulators, HCF1 and SET1

The chromatin factors SET-26 and HCF-1 oppose the histone deacetylase HDA-1 in longevity and gene regulation inC. elegans

“…SET-26 and its’ mammalian homolog, MLL5, have both been previously described to bind to the active H3K4me3 histone mark 15, 29 , which could account for their method of recruitment to chromatin. HCF-1 however, does not possess any DNA or chromatin binding domains itself, and the mammalian homolog is often recruited by other chromatin factors, including MLL5 16, 30 , to large protein complexes. To determine whether SET-26 could recruit HCF-1 to chromatin in somatic cells of C. elegans , we obtained the chromatin binding profile of HCF-1 using our HCF-1-tagged strain in germline-less worms with and without functional set-26 .…”

“…Because SET-26 and HCF-1 homologs are well known to work in large complexes of chromatin factors 23, 26, 30, 31 , we wondered whether we could identify additional protein factors that might work together with SET-26 and HCF-1 at chromatin in C. elegans . We returned to the IP-Mass Spec for C. elegans HCF-1 interactors and were particularly interested to find the histone deacetylase HDA-1, homolog of mammalian HDAC1 and HDAC2.…”

“…While we have not completely ruled out an indirect effect caused by loss of set-26 , it is tempting to speculate that SET-26 may directly recruit HCF-1 to chromatin. This is especially intriguing given evidence from human cells that mammalian homologs, MLL5 and HCF-1, directly interact 23, 30 , and recent work that showed MLL5 was required for proper HCF-1 recruitment at certain MLL5 target genes 30 . It will be interesting in the future to determine whether the highly conserved “HCF-1 binding motif” identified in the human MLL5 protein 23 is also required for the interaction between C. elegans SET-26 and HCF-1.…”

“…Given the conserved relationship between SET-26 and HCF-1 homologs in humans 23, 30 and the conservation of SET-26, HCF-1, and HDA-1 homologs in regulating mitochondria in mammals 13, 27, 31, 42 , it will be interesting to further explore the role between these three factors in mammalian cells, especially in respect to the regulation of mitochondrial gene expression. As all three factors in humans are implicated in neurodevelopment 37, 38, 45 and cancer 39–41 , and HCF-1’s function in cancer has already been linked to the regulation of mitochondrial gene expression 31 , understanding how MLL5, HCF-1, and HDAC1/2 interact and the pathways they regulate in humans could have broad implications for understanding both aging and human disease.…”

Upregulation of HCFC1 expression promoted hepatocellular carcinoma progression through inhibiting cell cycle arrest and correlated with immune infiltration

“…Quintana AM reported that HCFC1 was the key gene to regulating craniofacial development [20]. HCFC1 also plays a non-negligible role in various types of cancers, such as renal cell carcinoma, cervical cancer, prostate cancer, and myeloid malignancies [21][22][23]. Dysfunctions of HCFC1-dependent pathways which were regulated by gene regulation by insulin were closely related to tumorigenesis and progression [24].…”