MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis

Zhai Q, Luo M, Zhang Y, Zhang W, Wu C, Lv S, Wei Q. Histone methyltransferase KMT2D mediated lipid metabolism via peroxisome proliferator-activated receptor gamma in prostate cancer. Transl Cancer Res. 2022 Aug;11(8):2607–21. PMID: 36093518; PMCID: PMC9459503.; Jang Y, Broun A, Wang C, Park YK, Zhuang L, Lee JE, Froimchuk E, Liu C, Ge K. H3.3K4M destabilizes enhancer H3K4 methyltransferases MLL3/MLL4 and impairs adipose tissue development. Nucleic Acids Res. 2019 Jan 25;47(2):607–20. PMID: 30335158; PMCID: PMC6344897.; Kim DH, Kim J, Kwon JS, Sandhu J, Tontonoz P, Lee SK, Lee S, Lee JW. Critical Roles of the Histone Methyltransferase MLL4/KMT2D in Murine Hepatic Steatosis Directed by ABL1 and PPAR?2. Cell Rep. 2016 Nov 01;17(6):1671–82. doi: 10.1016/j.celrep.2016.10.023. PMID: 27806304.; Hardy T, Oakley F, Anstee QM, Day CP. Nonalcoholic Fatty Liver Disease: Pathogenesis and Disease Spectrum. Annu Rev Pathol. 2016 May 23;11():451–96. doi: 10.1146/annurev-pathol-012615-044224. PMID: 26980160.; Yu P, Ji L, Lee KJ, Yu M, He C, Ambati S, McKinney EC, Jackson C, Baile CA, Schmitz RJ, Meagher RB. Subsets of Visceral Adipose Tissue Nuclei with Distinct Levels of 5-Hydroxymethylcytosine. PLoS ONE. 2016 May 12;11(5):e0154949. doi: 10.1371/journal.pone.0154949.; Cho YW, Hong S, Jin Q, Wang L, Lee JE, Gavrilova O, Ge K. Histone methylation regulator PTIP is required for PPARgamma and C/EBPalpha expression and adipogenesis. Cell Metab. 2009 Jul;10(1):27–39. PMID: 19583951; PMCID: PMC2732027.; Lee J, Saha PK, Yang QH, Lee S, Park JY, Suh Y, Lee SK, Chan L, Roeder RG, Lee JW. Targeted inactivation of MLL3 histone H3-Lys-4 methyltransferase activity in the mouse reveals vital roles for MLL3 in adipogenesis. Proc Natl Acad Sci U S A. 2008 Dec 09;105(49):19229–34. PMID: 19047629; PMCID: PMC2614744.; Nielsen R, Pedersen TA, Hagenbeek D, Moulos P, Siersbaek R, Megens E, Denissov S, Børgesen M, Francoijs KJ, Mandrup S, Stunnenberg HG. Genome-wide profiling of PPARgamma:RXR and RNA polymerase II occupancy reveals temporal activation of distinct metabolic pathways and changes in RXR dimer composition during adipogenesis. Genes Dev. 2008 Nov 01;22(21):2953–67. PMID: 18981474; PMCID: PMC2577787.; Lee S, Lee J, Lee S, Lee JW. Activating Signal Cointegrator-2 Is an Essential Adaptor to Recruit Histone H3 Lysine 4 Methyltransferases MLL3 and MLL4 to the Liver X Receptors. Molecular Endocrinology. 2008 Jun;22(6):1312–9. doi: 10.1210/me.2008-0012.

Metabolites

ATP(4-)

Formula: C10H12N5O13P3 (502.9644492)

CAS ID:

ADP(3-)

Formula: C10H12N5O10P2 (424.0059412)

CAS ID:



Enzyme

EC Number name full name note
2.3.1.-
1.14.11.68 [histone H3]-trimethyl-L-lysine27 demethylase [histone H3]-N6,N6,N6-trimethyl-L-lysine27,2-oxoglutarate:oxygen oxidoreductase
1.14.19.1 stearoyl-CoA 9-desaturase stearoyl-CoA,ferrocytochrome-b5:oxygen oxidoreductase (9,10-dehydrogenating)
2.3.1.15 glycerol-3-phosphate 1-O-acyltransferase acyl-CoA:sn-glycerol-3-phosphate 1-O-acyltransferase
2.3.1.199 very-long-chain 3-oxoacyl-CoA synthase malonyl-CoA:very-long-chain acyl-CoA malonyltransferase (decarboxylating and thioester-hydrolysing)
2.3.1.20 diacylglycerol O-acyltransferase acyl-CoA:1,2-diacyl-sn-glycerol O-acyltransferase
2.3.1.286 protein acetyllysine N-acetyltransferase [protein]-N6-acetyl-L-lysine:NAD+ N-acetyltransferase (NAD+-hydrolysing; 2''-O-acetyl-ADP-D-ribose-forming)
2.3.1.51 1-acylglycerol-3-phosphate O-acyltransferase acyl-CoA:1-acyl-sn-glycerol-3-phosphate 2-O-acyltransferase
2.3.1.76 retinol O-fatty-acyltransferase acyl-CoA:retinol O-acyltransferase
2.7.10.2 non-specific protein-tyrosine kinase ATP:[protein]-L-tyrosine O-phosphotransferase (non-specific)
2.7.11.1 non-specific serine/threonine protein kinase ATP:protein phosphotransferase (non-specific)
2.7.11.2 [pyruvate dehydrogenase (acetyl-transferring)] kinase ATP:[pyruvate dehydrogenase (acetyl-transferring)] phosphotransferase
2.7.11.22 cyclin-dependent kinase ATP:cyclin phosphotransferase
2.7.11.23 [RNA-polymerase]-subunit kinase ATP:[DNA-directed RNA polymerase] phosphotransferase
3.1.1.23 acylglycerol lipase glycerol-ester acylhydrolase
3.1.1.3 triacylglycerol lipase triacylglycerol acylhydrolase
3.1.1.32 phospholipase A1 phosphatidylcholine 1-acylhydrolase
3.1.1.34 lipoprotein lipase triacylglycero-protein acylhydrolase
3.1.1.4 phospholipase A2 phosphatidylcholine 2-acylhydrolase
3.1.1.79 hormone-sensitive lipase diacylglycerol acylhydrolase
3.1.3.4 phosphatidate phosphatase diacylglycerol-3-phosphate phosphohydrolase
3.5.1.98 histone deacetylase histone amidohydrolase
6.2.1.1 acetate-CoA ligase acetate:CoA ligase (AMP-forming)
6.2.1.15 arachidonate-CoA ligase arachidonate:CoA ligase (AMP-forming)
6.2.1.17 propionate-CoA ligase propanoate:CoA ligase (AMP-forming)
6.2.1.24 phytanate-CoA ligase phytanate:CoA ligase (AMP-forming)
6.2.1.3 long-chain-fatty-acid-CoA ligase long-chain fatty acid:CoA ligase (AMP-forming)


Proteins

Protein ID name full name