LMCD1/Dyxin is a novel transcriptional cofactor that restricts GATA6 function by inhibiting DNA binding.
The activity of GATA factors is regulated, in part, at the level of protein-protein interactions. LIM domain proteins, first defined by the zinc finger motifs found in the Lin11, Isl-1, and Mec-3 proteins, act as coactivators of GATA function in both hematopoietic and cardiovascular tissues. We have identified a novel GATA-LIM interaction between GATA6 and LMCD1/dyxin. The LIM domains and cysteine-rich domains in LMCD1/dyxin and the carboxy-terminal zinc finger of GATA6 mediate this interaction. Expression of LMCD1/dyxin is remarkably similar to that of GATA6, with high-level expression observed in distal airway epithelium of the lung, vascular smooth muscle, and myocardium. In contrast to other GATA-LIM protein interactions, LMCD1/dyxin represses GATA6 activation of both lung and cardiac tissue-specific promoters. Electrophoretic mobility shift and chromatin immunoprecipitation assays show that LMCD1/dyxin represses GATA6 function by inhibiting GATA6 DNA binding. These data reveal an interaction between GATA6 and LMCD1/dyxin and demonstrate a novel mechanism through which LIM proteins can assert their role as transcriptional cofactors of GATA proteins.
Rath
Nibedita
N
Department of Medicine, University of Pennsylvania, Philadelphia, 19104, USA.
Wang
Zhishan
Z
Lu
Min Min
MM
Morrisey
Edward E
EE
D021581:Active Transport, Cell Nucleus; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056970:Co-Repressor Proteins; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D005318:Fetal Heart / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D066298:In Vitro Techniques; D060588:LIM Domain Proteins; D008168:Lung / Q000196:embryology / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D056970:Co-Repressor Proteins; D060588:LIM Domain Proteins; C485786:Lmcd1 protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D014157:Transcription Factors; D004247:DNA