TY  - JOUR
A1  - Serfling, Edgar
A1  - Rudolf, Ronald
A1  - Busch, Rhoda
A1  - Patra, Amiya K.
A1  - Muhammad, Khalid
A1  - Avots, Andris
A1  - Andrau, Jean-Christophe
A1  - Klein-Hessling, Stefan
T1  - Architecture and expression of the Nfatc1 gene in lymphocytes
N2  - In lymphocytes, the three NFAT factors NFATc1 (also designated as NFAT2), NFATc2 (NFAT1), and NFATc3 (NFAT4 or NFATx) are expressed and are the targets of immune receptor signals, which lead to a rapid rise of intracellular Ca++, the activation of phosphatase calcineurin, and to the activation of cytosolic NFATc proteins. In addition to rapid activation of NFAT factors, immune receptor signals lead to accumulation of the short NFATc1/αA isoform in lymphocytes which controls their proliferation and survival. In this mini-review, we summarize our current knowledge on the structure and transcription of the Nfatc1 gene in lymphocytes, which is controlled by two promoters, two poly A addition sites and a remote downstream enhancer. The Nfatc1 gene resembles numerous primary response genes (PRGs) induced by LPS in macrophages. Similar to the PRG promoters, the Nfatc1 promoter region is organized in CpG islands, forms DNase I hypersensitive sites, and is marked by histone tail modifications before induction. By studying gene induction in lymphocytes in detail, it will be important to elucidate whether the properties of the Nfatc1 induction are not only typical for the Nfatc1 gene but also for other transcription factor genes expressed in lymphocytes.
KW  - transcription
KW  - chromatin
KW  - induction
KW  - lymphocytes
KW  - Nfatc1
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-112718
ER  - 
TY  - JOUR
A1  - Klein-Hessling, Stefan
A1  - Rudolf, Ronald
A1  - Muhammad, Khalid
A1  - Knobeloch, Klaus-Peter
A1  - Maqbool, Muhammad Ahmad
A1  - Cauchy, Pierre
A1  - Andrau, Jean-Christophe
A1  - Avots, Andris
A1  - Talora, Claudio
A1  - Ellenrieder, Volker
A1  - Screpanti, Isabella
A1  - Serfling, Edgar
A1  - Patra, Amiya Kumar
T1  - A threshold level of NFATc1 activity facilitates thymocyte differentiation and opposes notch-driven leukaemia development
JF  - Nature Communications
N2  - NFATc1 plays a critical role in double-negative thymocyte survival and differentiation. However, the signals that regulate Nfatc1 expression are incompletely characterized. Here we show a developmental stage-specific differential expression pattern of Nfatc1 driven by the distal (P1) or proximal (P2) promoters in thymocytes. Whereas, preTCR-negative thymocytes exhibit only P2 promoter-derived Nfatc1β expression, preTCR-positive thymocytes express both Nfatc1β and P1 promoter-derived Nfatc1α transcripts. Inducing NFATc1α activity from P1 promoter in preTCR-negative thymocytes, in addition to the NFATc1β from P2 promoter impairs thymocyte development resulting in severe T-cell lymphopenia. In addition, we show that NFATc1 activity suppresses the B-lineage potential of immature thymocytes, and consolidates their differentiation to T cells. Further, in the pTCR-positive DN3 cells, a threshold level of NFATc1 activity is vital in facilitating T-cell differentiation and to prevent Notch3-induced T-acute lymphoblastic leukaemia. Altogether, our results show NFATc1 activity is crucial in determining the T-cell fate of thymocytes.
KW  - acute lymphocytic leukaemia
KW  - transcription factors
KW  - lymphocyte differentiation
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172974
VL  - 7
ER  -