Sumoylation modulates a domain in CTCF that activates transcription and decondenses chromatin.
CTCF is a multipurpose transcription factor with activation, repression, and insulator activity. It also participates in regulating chromatin architecture by maintaining open chromatin and mediating long-range chromosomal interactions. Participation by CTCF in such diverse processes suggests that it has multiple functional domains that regulate transcription and modify chromatin structure. Using transient and integrated reporters, we identified a 107-amino-acid domain in CTCF's N-terminal region that is capable of transcriptional activation and chromatin decondensation. This domain demonstrated moderate transactivation when targeted to a promoter proximal position but showed little activity from more distal positions and on a natural promoter. By contrast, the activation domain dramatically decondensed the compact chromatin structure of a large transgene array, in a manner similar to the potent activation domain in VP16. In addition, the activation domain is subject to conjugation by SUMO, which reduced its transcriptional and chromatin opening activity. Moreover, mimicking full sumoylation by fusing Sumo-1 or -3 to the activation domain eliminated its transcriptional activity, but only Sumo-3 fusion prevented chromatin opening. We suggest that the activation domain's limited transactivation, but strong chromatin decondensation allows CTCF to establish and maintain open chromatin without necessarily activating transcription. Sumoylation may contribute to CTCF's enhancer blocking or repression functions by reducing transactivation and chromatin opening.
Kitchen
Neal S
NS
Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Schoenherr
Christopher J
CJ
D000818:Animals; D000076246:CCCTC-Binding Factor; D002460:Cell Line; D002843:Chromatin; D042002:Chromatin Assembly and Disassembly; D006801:Humans; D051379:Mice; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D058207:Sumoylation / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D002843:Chromatin; C000619698:Ctcf protein, mouse; D012097:Repressor Proteins