For mRNA-seq, total RNA was directly extracted from cells cultured in 3.5 cm dishes by TRIzol reagent with two biological replicates for each cell line. For ChIP-seq, Cells were harvested in PBS and cross-linked with 1% formaldehyde for 9 min at room temperature, cells prepared for RNA pol II were pre-cross-linked with 0.2 mM disuccinimidyl glutarate (DSG, ProtecoChem, c1104) for 30 min at room temperature. Reaction was terminated by adding glycine to a final concentration of 125 mM, incubated at room temperature for 5 min. After washing with PBS twice, cells were resuspended in 5 mL of Lysis Buffer 1 (50 mM HEPES, pH 7.9, 140 mM NaCl, 1 mM EDTA, 10% glycerol, 0.5% NP-40, 0.25%Triton X-100), incubated on ice for 10 min. After centrifuge at 2,000 rpm at 4 ˚C for 5 min, cells were then resuspended in 5 mL of Lysis Buffer 2 (10 mM Tris-HCl, pH8.0, 200 mM NaCl, 1 mM EDTA and 0.5 mM EGTA), incubated at room temperature for 10 min. The lysate was centrifuged at 4,000 rpm for 5 min at 4 ˚C. The chromatin fraction was resuspended in 1 mL of Lysis Buffer 3 (10 mM Tris-HCl, pH 8.0, 100 mM NaCl, 1 mM EDTA, 0.5 mM EGTA, 0.1% sodium deoxycholate and 0.5% sodium N-lauroylsarcosine, 1x proteinase inhibitor (Merck, 5892970001)). Chromatin was then sonicated into 200-400 bp fragments (Covaris M220), in assistance with 0.1% sodium dodecyl sulfate (SDS) or 0.5% SDS (for double cross-linked sample). Supernatant after centrifuging at 12,000 rpm for 10 min at 4 ˚C were flash freezed and kept in -80 ˚C refrigerator. Keep 10% of chromatin as input, the fragments were immunoprecipitated overnight with antibodies against histone modifications or RNA pol II. Pre-washed Dynabeads protein A or G (ThermoFisher 10002D, or 10004D) was added to the Protein-antibody complexes, and incubated at 4 ˚C for 1 hour. The beads were sequentially washed with buffers as follows: FA-lysis buffer (150 mM NaCl, 1% Triton X-100, 50 mM HEPES, pH 7.9, 2 mM EDTA and 0.5 mM sodium deoxycholate), FA high salt buffer (500 mM NaCl, 1% Triton X-100, 50 mM HEPES, pH 7.9, 2 mM EDTA and 0.5% sodium deoxycholate) for twice, LiCl buffer (250 mM LiCl, 0.5% NP-40, 0.5% sodium deoxycholate, 1 mM EDTA and 10 mM Tris-HCl, pH 8.0), TE buffer (10 mM Tris-HCl, pH8.0, 1 mM EDTA) for twice. Each washing step was incubated for 5 min at 4 ˚C with rotation. Protein-DNA complexes were eluted by incubation with 250 µl of elution buffer (1% SDS, 100 mM NaHCO3, freshly made) for 15 min at 55 ˚C with periodic gentle vortex. This step was repeated once and eluted sample was combined. Eluted DNA, as well as input, was reverse cross-linked from protein by adding 20 µl of 5M NaCl to the 500 µl of elution, incubated at 65 ˚C over 8 hours. After digested with RNase at 37 ˚C, proteinase K at 55 ˚C, DNA was extracted by phenol-chloroform method. RNA-seq library construction: Poly-A tailed mRNA molecules were captured using attached oligo-dT and subjected to library construction according to the manufacturer's recommendations. The ChIP-seq libraries were constructed using NEBNext DNA Sample Prep Master Mix (NEB).DNA libraries were subjected to size-selection using AMPure XP beads (Beckman Coulter) and PCR amplification (18-20 cycles for ChIP-seq DNA libraries).