TABLE 2.

A non-exhaustive list of transcriptional targets of Grh/GRHL factors in literature.

Target gene	Binding region	Species/Model	Regulated by GRHL	Activation/Repression	Function	References
Dopa decarboxylase (Ddc)	Promoter/Enhancer	Drosophila	Grainyhead	Activation	Hardening of larval and adult cuticles	Bray and Kafatos, 1991; Venkatesan et al., 2003; Mace et al., 2005
Ultrabithorax (Ubx)	Promoter	Drosophila	Grainyhead	Activation	Differentiation of ‘head skeleton’	Bray and Kafatos, 1991
Engrailed (en)	Promoter	Drosophila	Grainyhead	Activation	Posterior wing compartment identity	Soeller et al., 1988
Zerknüllt (zen), Tailless (tll), Scute (sc), Sex lethal (Sxl)	Promoter	Drosophila	Grainyhead	Repression	Developmental patterning, sex determination and cellularization	Harrison et al., 2010
Fasciclin 3 (Fas3), Coracle (cora), Sinuous (Sinu)	Intron 1	Drosophila	Grainyhead	Activation	Septate junction proteins that forms barrier epithelia	Narasimha et al., 2008
Stitcher (stit)	Intron 2	Drosophila	Grainyhead	Activation	Epidermal wound healing	Wang et al., 2009
Misshapen (msn), Krotzkopf verkehrt (kkv), Tyrosine hydroxylase (ple)	Enhancer	Drosophila	Grainyhead	Activation	Epidermal wound healing	Pearson et al., 2009
Claudin b (cldnb), Epithelial cell adhesion molecule (epcam)	Enhancer	Zebrafish	Grhl2b	Activation	Otic development and hearing ability	Han et al., 2011
Engrailed 2a (eng2a), CDC42 small effector 1 (cdc42se1)	Promoter	Zebrafish	Grhl2b	Activation	Midbrain-hindbrain morphogenesis	Dworkin et al., 2012
Engrailed-1 (EN1)	Promoter	Human	GRHL1	Activation	Morphogenesis	Wilanowski et al., 2002
Desmoglein 1 (Dsg1/DSG1)	Promoter	Human and Mouse	GRHL1	Activation	Desmosome organization	Wilanowski et al., 2008
Albumin (Alb), Carbamoylphosphate synthetase I (1), Hepatocyte nuclear factor 4α (Hnf4α), CCAAT/enhancer binding protein α (Cebpa)	Unknown	Mouse	Grhl2	Repression	Inhibition of hepatocytic differentiation	Tanimizu et al., 2013
Claudin 3 (Cldn3), Claudin 4 (Cldn4), E-cadherin (Cdh1)	Promoter – Cldn4, Intron 2 – Cdh1	Mouse	Grhl2	Activation	Maintenance of breast epithelial cell identity	Werth et al., 2010
miR-122	Promoter	Human	GRHL2	Repression	Ethanol induced liver injury and fibrosis	Satishchandran et al., 2018
miR-200b/-200a/429	Promoter	Human	GRHL2	Activation	Suppression of EMT	Cieply et al., 2012; Chung et al., 2016
Serine peptidase inhibitor, Kunitz type 1 (SPINT1)	Promoter	Human	GRHL2	Activation	Salivary gland development	Walentin et al., 2015; Matsushita et al., 2018
Matrix metalloproteinases (MMPs) - multiple	Unknown	Human	GRHL2	Repression	Suppression of invasion phenotype	Chung et al., 2016; Pifer et al., 2016; Xiang et al., 2017
Forkhead box M1B (FOXM1B)	Promoter	Human	GRHL2	Activation	Human papillomavirus associated oropharyngeal cancer development	Chen et al., 2018c, 2
Tumor protein p63 (TP63/p63)	Promoter	Human	GRHL2	Activation	Maintenance of epithelial phenotype in human keratinocytes	Mehrazarin et al., 2015
Ovo like zinc finger 2 (Ovol2/OVOL2)	Promoter	Human and Mouse	GRHL2	Activation	Epithelial barrier function and palatogenesis	Watanabe et al., 2014; Aue et al., 2015; Carpinelli et al., 2020
v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3 (Erbb3/ERBB3)	Promoter	Human and Mouse	GRHL2	Activation	Suppression of EMT	Werner et al., 2013; Chung et al., 2016
member RAS oncogene family (Rab25/RAB25)	Promoter	Human and Mouse	GRHL2	Activation	Regulation of epithelial morphogenesis	Senga et al., 2012; Gao et al., 2013
Rho Guanine Nucleotide Exchange Factor 19 (Arhgef19/ARHGEF19)	Promoter	Human and Mouse	GRHL2 and GRHL3	Activation	Maintenance of epidermal differentiation	Caddy et al., 2010; Boglev et al., 2011; Gao et al., 2013
miR-21	Promoter	Human and Mouse	GRHL3	Repression	Maintenance of epidermal differentiation	Bhandari et al., 2013
Transglutaminase 1 (Tgm1/TGM1)	Promoter	Human and Mouse	GRHL3	Activation	Maintenance of epidermal differentiation	Ting et al., 2005; Boglev et al., 2011
Uroplakin 2 (UpkII)	Promoter	Mouse	GRHL3	Activation	Urothelial differentiation	Yu et al., 2009