ZXDC, a novel zinc finger protein that binds CIITA and activates MHC gene transcription.
The class II trans-activator (CIITA) is recognized as the master regulator of major histocompatibility complex (MHC) class II gene transcription and contributes to the transcription of MHC class I genes. To better understand the function of CIITA, we performed yeast two-hybrid with the C-terminal 807 amino acids of CIITA, and cloned a novel human cDNA named zinc finger, X-linked, duplicated family member C (ZXDC). The 858 amino acid ZXDC protein contains 10 zinc fingers and a transcriptional activation domain, and was found to interact with the region of CIITA containing leucine-rich repeats. Over-expression of ZXDC in human cell lines resulted in super-activation of MHC class I and class II promoters by CIITA. Conversely, silencing of ZXDC expression reduced the ability of CIITA to activate transcription of MHC class II genes. Given the specific interaction between the ZXDC and CIITA proteins, as well as the effect of ZXDC on MHC gene transcription, it appears that ZXDC is an important regulator of both MHC class I and class II transcription.
Al-Kandari
Wafa
W
Department of Biological, Geological and Environmental Sciences, 2121 Euclid Ave., SI219, Cleveland State University, Cleveland, OH 44115, United States.
Jambunathan
Srikarthika
S
Navalgund
Vandana
V
Koneni
Rupa
R
Freer
Margot
M
Parimi
Neeta
N
Mudhasani
Rajini
R
Fontes
Joseph D
JD
D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D015534:Trans-Activators / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000276:immunology; D016335:Zinc Fingers
D018076:DNA, Complementary; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C516737:ZXDC protein, human