MLL histone methylases in gene expression, hormone signaling and cell cycle

Abstract

Histone methyl-transferases (HMTs) are key enzymes that post-translationally methylate nuclear histone proteins and play critical roles in gene expression, epigenetic regulation and diseases in eukaryotic organisms. Mixed lineage leukemias (MLLs) are human HMTs that specifically methylate histone H3 at lyisine-4 and regulate gene activation. MLLs are also well known to be rearranged often in acute myeloid and lymphoid leukemias. Human encodes several MLLs that have similar enzymatic activities but diverse functions. Herein, we have reviewed the recent advances in understanding the diverse functions of MLL family of HMTs in gene regulation, hormone signaling and cell cycle regulation in human.

Global Gene Expression Analysis in Cord Blood Reveals Gender-Specific Differences in Response to Carcinogenic Exposure In Utero

“…Not all genes conclusively point to a male predisposition for developing ALL, in fact we found a female-specific-positive correlation of MllT6. Mixed lineage leukemias are histone methyl-transferases that regulate gene activation and are also well known to be rearranged in acute myeloid and lymphoid leukemias (48). Interestingly, the female-specific correlation might be in line with the literature.…”

“…Concordantly, differentially correlating leukemia and lymphoma genes with AR receptor activation do not conclusively support a male predisposition. In fact, next to the MLLT6 gene correlating with the ERa receptor, a female-specific positive correlation of MllT3 with AR receptor activation was found which might be related to female predisposition to develop infant leukemia (37,48,49).…”

Bisphenol-A induces expression of HOXC6, an estrogen-regulated homeobox-containing gene associated with breast cancer

“…Notably, MLLs are well-known human histone H3K4-specific methyl-transferases that play key roles in gene activation (51, 71). There are several MLLs: MLL1, MLL2, MLL3, MLL4 and MLL5 (51, 71).…”

“…Notably, MLLs are well-known human histone H3K4-specific methyl-transferases that play key roles in gene activation (51, 71). There are several MLLs: MLL1, MLL2, MLL3, MLL4 and MLL5 (51, 71). Recent studies from our (and others) laboratory demonstrated that MLLs (MLL1–4) acts as ER-coregulators and associated with ER-mediated gene activation (14, 15, 45, 49, 63, 69).…”

“…Recent studies from our (and others) laboratory demonstrated that MLLs (MLL1–4) acts as ER-coregulators and associated with ER-mediated gene activation (14, 15, 45, 49, 63, 69). MLLs (MLL1–4) contains one or more LXXLL (nuclear receptor box or NR-box) domains through which they interact with nuclear receptors (NRs), get recruited to the NR-regulated gene promoters, introduces H3K4-trimethylation leading to gene activation (51, 71). Here, our results demonstrated that along with ERs, histone methylases MLL2 and MLL3, are enriched at the HOXC6 promoter upon treatment with E2 and BPA.…”