Table 2.

Transcriptional regulators of CLN3

Putative Transcriptional Regulator	Protein details	Putative effect	Methods used to identify putative transcriptional regulator	References
AP‐2A	Putative CLN3 promoter has an AP‐2A binding site.	Putative CLN3 promoter has an AP‐2A binding site.	The authors developed a computational genomics strategy termed ChIPModules which begins with experimentally‐determined binding sites and integrates those with positional weight matrices constructed from transcription factor binding sites, comparative genomics, and statistical learning methods with the purpose of identifying transcriptional regulatory modules. They identify that the putative CLN3 promoter contains an AP‐2alpha binding site	Jin, Rabinovich, Squazzo, Green, and Farnham (2006)
E2F1	E2F1_HUMAN	Putative CLN3 promoter has a putative E2F1 binding site.	Researchers studied the binding of E2F1 to promoters. ChIP analyses of 24,000 promoters confirmed that more than 20% of promoters are bound by E2F1. Including the CLN3 promoter	Bieda, Xiaoqin, Singer, Green, and Farnham (2006)
ELAV1 (huR)E2F1	E2F1_HUMAN	Putative CLN3 promoter has a putative E2F1 binding site.	HuR regulates the stability and translation of numerous mRNAs encoding for stress response and proliferative proteins. HuR was found to bind CLN3 mRNA. The interaction value was higher than the mock controls; albeit very weak. Researchers studied the binding of E2F1 to promoters. ChIP analyses of 24,000 promoters confirmed that more than 20% of promoters are bound by E2F1. Including the CLN3 promoter	Abdelmohsen et al. (2009); Bieda et al. (2006)
ETS1ELAV1 (huR)	ETS1 Human	ETS1 binds to the putative CLN3 promoter	The CLN3 promoter contains putative ETS1 binding motifs. HuR regulates the stability and translation of numerous mRNAs encoding for stress responses and proliferative proteins. HuR was found to bind CLN3 mRNA. The interaction value was higher than the mock controls; albeit very weak.	Hollenhorst et al. (2009); Abdelmohsen et al. (2009)
ETS1ETS1	ETS1 MouseETS1 Human	ETS1 binds to the putative CLN3 promoter	CLN3 is downregulated in ETS1‐/‐ mNK cells. The CLN3 promoter contains putative ETS1‐binding motifs.	Ramirez et al. (2012); Hollenhorst et al. (2009)
HNF4‐alphaETS1	HNF4A_HUMANETS1 Mouse	HNF4‐alpha binds to gene CLN3 promoterETS1	In the referenced paper, CLN3 appears in a list of potential HNF4alpha target genes in differentiated Caco2 colorectal adenocarcinoma cells. CLN3 is downregulated in ETS1‐/‐ mNK cells	Bolotin et al. (2010), Boyd, Bressendorff, Møller, Olsen, and Troelsen (2009) and Ramirez et al. (2012)
HSF1HNF4‐alpha	HSF1_HUMANHNF4A_HUMAN	CLN3 harbors an HSF 1 site I at a proximal Alu in an antisense orientationHNF4‐alpha binds to gene CLN3 promoter	CLN3 is downregulated upon heat shock in microarray experiments. In the referenced paper, CLN3 appears in a list of potential HNF4alpha target genes in differentiated Caco2 colorectal adenocarcinoma cells.	Bolotin et al. (2010), Boyd et al. (2009) and Pandey, Mandal, Jha, and Mukerji (2011)
TFEB	CLEAR	CLN3 harbors a two CLEAR binding site on its proximal promoter (at −24 nad +6).	TFEB has been shown to bind this (CLEAR) element in the proximal promoter of CLN3 and increase CLN3 transcription.	Palmieri et al. (2011) and Sardiello et al. (2009)