Table 1.

Roles of ATP-dependent chromatin remodeling factors in cardiovascular development and disease

Class	Chromatin Remodeling Factor	Cardiovascular Studies in Animals		Comment	Ref
		Tissue of Gene Modification	Phenotype
SWI/SNF	BRG1	Deletion in endothelium and endocardium	Lethality at E10.5–E11.5. Hypotrabeculation, yolk sac vascular defects, anemia.	Brg1 represses endocardial Adamts1 to prevent premature degradation of cardiac jelly, essential for trabeculation.	10
		Deletion in myocardium	Lethality at E11.5. Thin compact myocardium and absent IVS*	Brg1 maintains Bmp10 to promote myocardial proliferation in embryos. Brg1 associates with HDACs and PARPs to repress α-MHC and activate β-MHC in embryonic hearts.	17
			Inducible Brg1 deletion in adult myocardium prevents cardiac hypertrophy and fibrosis.	Cardiac stress activates Brg1, which then associates with HDACs and PARPs to control the pathological MHC switch, hypertrophy and fibrosis.	17
		Deletion in secondary heart field	Lethality at E10.5. Hypoplastic right ventricle and outflow tract.	Brg1 maintains Bmp10 to promote proliferation of right ventricular and outflow tract myocardium.	17
		Heterozygous germline mutation Brg1+/−	Variable heart defects: VSD*, patent foramen ovale, cardiac dilatation, sinus node dysfunction, AV block, conduction abnormalities.	Brg1 interacts dose-dependently with Nkx2.5, Tbx5, and Tbx20 to regulate heart development.	*
		Point mutation; Morpholino knockdown in zebrafish	Mutation of brg1 in zebrafish causes hypoplastic myocardium, abnormal shape and alignment of cardiomyocytes. Knockdown causes cardiac looping defects, chamber narrowing, and contractility reduction.	Brg1 is evolutionarily conserved in zebrafish heart development.	*
	BAF180	Germline deletion	Lethality at E12.5–15.5. Thin compact myocardium, hypoplastic ventricles, VSD*, coronary defects.	Baf180 interacts with the retinoid acid pathway to regulate cardiac chamber formation. Baf180 is required for expression of genes essential for coronary vessel formation.	38, 41
	BAF60c	Knockdown in mouse hearts	Lethality at E10.0–11.0. Hypoplastic ventricles, hypotrabeculation, shortened outflow tract, abnormal cardiac looping.	Baf60c regulates heart morphogenesis through Hand2, Bmp10, Irx3 and others. Baf60c controls cardiac looping by activating Notch signaling and Nodal expression.	42, 43
		Knockdown in zebrafish	Randomized cardiac looping.	Zebrafish and mouse Baf60c share conserved functions for heart looping regulation.	43
	BAF45c	Knockdown in zebrafish	Abnormal cardiac looping, poorly defined AV* boundary, reduced cardiac contractility, disarrayed muscle fibers.	Baf45c recognizes acetylated and methylated histones. This recognition may recruit BRG1/BAF to muscle- relevant gene promoters.	45, 46
ISWI	SNF2H	Germline deletion	Lethality at E5.5–7.5 due to growth failure of the inner cell mass and trophoblast.	Snf2h may regulate heart development through the Wstf-containing WICH complex.	51, 59
CHD	CHD7	Heterozygous germline mutation Chd7+/−	Aortic arch interruptions due to hypoplastic 4th pharyngeal arch artery.	Chd7 interacts with Tbx1 to regulate aortic arch formation in mice.	61, 62
		Knockdown; Expression of dominant-negative Chd7 in frog	Abnormal position of truncus arteriosus and cardiac outflow tract.	CHD7 associates with BRG1/PBAF to control Sox9, Twist, Slug and neural crest cell activation.	48
INO80	REPTIN PONTIN	Activation of repin or knockdown of pontin in zebrafish	Cardiac muscle hyperplasia.	Pontin and Reptin antagonistically control heart muscle growth, in part, through the β-catenin pathway.	68

^*B. Bruneau: personal communication. ASD: atrial septal defect. AV: atrioventricular. IVS: interventricular septum. VSD: ventricular septal defect.