BioMed Research International

Research Article

The Transcription Factor ATF4 Promotes Expression of Cell Stress Genes and Cardiomyocyte Death in a Cellular Model of Atrial Fibrillation

Table 1

Genes regulated by ATF4. (a) List of top 45 genes being up- or downregulated in stimulated (S) HL-1 cardiomyocytes overexpressing ATF4wt (corresponding to Figure 3(a)). (b) List of top 48 genes that are regulated in cardiomyocytes overexpressing ATF4wt but not in HL-1 cells with overexpressing ATF4ΔRK detected by ChIP assay (corresponding to the grey area in Figure 4(b)). (c) Genes being up- or downregulated by stimulation in cardiomyocytes overexpressing ATF4wt detected by microarray and enrichment in ChIP assay of HL-1 cardiomyocytes overexpressing ATF4wt (corresponding to the grey area in Figure 4(c)).

(a)


Array ATF4wt stim versus GFP stim
Gene Symbol	fold change	1/ value

Saa3	16.40	2.78E − 34
Avil	10.58	6.34E − 07
Gsta3	3.39	3.98E − 03
Gadd45a	3.22	7.62E − 22
Serpinf1	2.96	1.67E − 17
Csn3	2.69	2.78E − 34
Lcn2	2.69	4.88E − 04
Clec2e	2.59	1.67E − 17
Dgat2	2.51	1.43E − 07
Gulo	2.50	2.33E − 05
Hdc	2.44	1.73E − 02
Sprr2f	2.41	2.38E − 04
Colec11	2.40	3.51E − 03
Iyd	2.22	7.11E − 03
Iah1	2.21	2.07E − 05
Aqp9	2.17	1.29E − 06
Tg	2.13	2.49E − 02
Cox6a2	2.12	6.01E − 08
Was	2.11	2.86E − 05
Agpat9	2.08	4.97E − 03
Gp5	2.08	4.65E − 03
Reep6	2.07	1.93E − 03
ATF4	1.51	3.35E − 03
Ifit3	0.30	1.01E − 02
Irf7	0.38	1.57E − 07
Gbp3	0.40	1.31E − 02
Iigp2	0.43	2.06E − 07
Vwa5a	0.43	3.75E − 10
Igtp	0.43	2.71E − 02
Myadm	0.44	6.31E − 03
Lgals3bp	0.45	1.25E − 04
Parp14	0.45	8.69E − 03
Trim41	0.45	1.77E − 02
Galnt11	0.45	6.09E − 03
Batf2	0.47	4.82E − 06
Lgals9	0.49	1.72E − 02
Eif2ak2	0.50	4.89E − 04
Oas1b	0.50	3.76E − 03
Gbl	0.51	7.16E − 06
Irgb10	0.53	1.95E − 06
Tap1	0.53	3.22E − 02
Pln	0.53	1.46E − 05
Ifi35	0.54	7.86E − 06
Psmb9	0.54	4.91E − 04
Cxcl1	0.56	3.19E − 05
Wdr6	0.56	5.56E – 04

(b)


ChIP ATF4wt w/o ATF4dRK
Gene Symbol	value

Stk40	38.47
Ddit3	35.56
Arhgef33	35.47
BC071253	33.68
Herpud1	31.72
AK018753	29.82
Abcc8	27.51
AK140265	26.10
Gm13889	24.81
Gm10222	24.27
DQ539915	23.56
Rp9	22.95
Cox2	22.34
Atpase6	22.29
E2f4	21.63
Cytb	21.28
Atf3	20.76
Aars	20.29
Zxdc	20.02
Cebpb	17.44
Wnt3a	17.33
Rpn2	17.25
Atpase6	17.22
Ddr2	16.66
Siah2	16.34
Trim14	13.19
Apbb2	13.05
Eif1	11.93
Abhd11	11.57
Trmt12	11.27
Psat1	11.21
Pknox1	10.68
Med30	10.34
Abcc8	10.15
Mthfd2	10.08
Gars	10.04
Slc25a26	9.88
Nupr1	9.53
Nars	9.07
Fbln5	9.06
Trib3	8.14
Crip2	8.03
Asap1	7.97
Gm16197	7.93
Cebpg	7.81

(c)


Array ATF4wt and ChIP ATF4wt
Gene Symbol	fold change	1/ value

Asns	1.66	0.0002
Trib3	1.49	1.0000
Aars	1.38	0.0410
Psat1	1.37	1.0000
Aldh18a1	1.34	1.0000
Mthfd2	1.34	0.1265
Jdp2	1.33	0.8275
Eif2s2	1.31	0.1495
Rhbdd1	1.28	1.0000
Atad2	1.25	1.0000
Herpud1	1.23	1.0000
Nupr1	1.20	1.0000
S100a6	0.79	1.0000