Cytokine-like nuclear factor N-PAC

Definition:

Cytokine-like nuclear factor with chromatin gene reader activity involved in chromatin modification and regulation of gene expression. Acts as a nucleosome-destabilizing factor that is recruited to genes during transcriptional activation. Recognizes and binds histone H3 without a preference for specific epigenetic markers and also binds DNA. Interacts with KDM1B and promotes its histone demethylase activity by facilitating the capture of H3 tails, they form a multifunctional enzyme complex that modifies transcribed chromatin and facilitates Pol II transcription through nucleosomes. Stimulates the acetylation of 'Lys-56' of nucleosomal histone H3 (H3K56ac) by EP300. With GATA4, co-binds a defined set of heart development genes and coregulates their expression during cardiomyocyte differentiation. Regulates p38 MAP kinase activity by mediating stress activation of MAPK14/p38alpha and specifically regulating MAPK14 signaling. Indirectly promotes phosphorylation of MAPK14 and activation of ATF2. The phosphorylation of MAPK14 requires upstream activity of MAP2K4 and MAP2K6.

References:

[1]. Jing Fu, et al. Nuclear protein NP60 regulates p38 MAPK activity. J Cell Sci. 2006 Jan 1;119(Pt 1):115-23. [Content Brief]

[2]. Jia Fei, et al. NDF, a nucleosome-destabilizing factor that facilitates transcription through nucleosomes. Genes Dev. 2018 May 1;32(9-10):682-694. [Content Brief]

[3]. Barbara Gonzalez-Teran, et al. Transcription factor protein interactomes reveal genetic determinants in heart disease. Cell. 2022 Mar 3;185(5):794-814.e30. [Content Brief]

[4]. Chiara Marabelli, et al. A Tail-Based Mechanism Drives Nucleosome Demethylation by the LSD2/NPAC Multimeric Complex. Cell Rep. 2019 Apr 9;27(2):387-399.e7. [Content Brief]

[5]. Michiel Vermeulen, et al. Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers. Cell. 2010 Sep 17;142(6):967-80. [Content Brief]

[6]. Rui Fang, et al. LSD2/KDM1B and its cofactor NPAC/GLYR1 endow a structural and molecular model for regulation of H3K4 demethylation. Mol Cell. 2013 Feb 7;49(3):558-70. [Content Brief]

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