title: The zinc finger proteins ZXDA and ZXDC form a complex that binds CIITA and regulates MHC II gene transcription.
abstract: The transcription of major histocompatibility complex class II (MHC II) genes depends critically upon the activity of the class II trans-activator (CIITA) protein. We previously described a novel CIITA-binding protein named zinc finger X-linked duplicated family member C (ZXDC) that contributes to the activity of CIITA and the transcription of MHC II genes. Here, we examined the contribution of a closely related family member of ZXDC, the ZXDA protein, to MHC II gene transcription. ZXDA has a domain organization similar to ZXDC, containing ten zinc fingers and a transcriptional activation domain. Knockdown and overexpression of ZXDA demonstrated its importance in the transcriptional activation of MHC II genes. We found that ZXDA and ZXDC can self-associate, and also form a complex with each other. The regions of the two proteins that contain zinc fingers mediate these interactions. Importantly, we found that the ZXDA-ZXDC complex interacts with CIITA, rather than either protein alone. Given our additional finding that ZXDC is present at MHC II promoters in HeLa cells, prior to and after treatment with IFN-gamma, it appears that ZXDA and ZXDC form an important regulatory complex for MHC II gene transcription.
authors.affiliation: Department of Biological, Geological and Environmental Sciences, Cleveland State University, Cleveland OH 44115-2214, USA.
authors.forename: Wafa
authors.initials: W
authors.lastname: Al-Kandari
authors.forename: Rupa
authors.initials: R
authors.lastname: Koneni
authors.forename: Vandana
authors.initials: V
authors.lastname: Navalgund
authors.forename: Anastasiia
authors.initials: A
authors.lastname: Aleksandrova
authors.forename: Srikarthika
authors.initials: S
authors.lastname: Jambunathan
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Fontes
mesh_terms: D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D020868:Gene Silencing; D006684:HLA-DR Antigens / Q000235:genetics; D059805:HLA-DR alpha-Chains; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D005810:Multigene Family; D046912:Multiprotein Complexes; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D016335:Zinc Fingers
chemical_list: D006684:HLA-DR Antigens; D059805:HLA-DR alpha-Chains; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C521135:ZXDA protein, human; C516737:ZXDC protein, human; D007371:Interferon-gamma