*4.2. Accession Numbers*

HOTAIR: Gene ID: 100124700 MEG3: Gene ID: 55384 MLL1: Uniprot: Q03164 MLL2: Uniprot: Q9UMN6 MLL3: Uniprot: Q8NEZ4 MLL4: Uniprot: O14686

#### *4.3. Overexpression and Purification of MLL4 Protein Regions*

The same methods of protein overexpression and purification were used for both protein constructs, MLL43500–3630 and MLL44210–4280. DNA sequences coding for each protein were cloned into pET22b cloning vector. Induction was done for 4 h at 28 ◦C by 0.1 M IPTG, cells were pelleted by centrifugation (4000 rpm, 20 min, 4 ◦C) then lysed by sonication in lysis buffer (50 mM Tris, 200 mM NaCl, 0.5% Triton X-100 pH 8.0 and EDTA-free SIGMAFAST Protease

Inhibitor Cocktail Tablets), cell debris was removed by centrifugation (12,100 rpm, 40 min, 4 ◦C). The supernatant was filtered through 0.2 μm nitrocellulose filter then purified over HisTrap HP column on an AKTA Explorer system using a gradient elution of two buffers (Buffer A: 20 mM imidazole, 200 mM NaCl, 20 mM Tris. pH 7.5. Buffer B: 1 M imidazole, 200 mM NaCl, 20 mM Tris, pH 7.5). Representative purification results are shown on Supplementary Figure S7. The mostly disordered nature of the MLL44210–4280 region was highlighted by its appearance at a larger size than its actual molecular weight (17 kDa vs. 7 kDa). Elution fractions containing sufficiently pure proteins were dialyzed against distilled water then lyophilized and stored at −20 ◦C. Lyophilized proteins were dissolved before use in ultrapure water or the appropriate assay buffer. The identity of the purified proteins was confirmed by mass spectrometry.
