EGR1 and NAB co-repressors bind EGR1 gene

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Homo sapiens
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EGR1 expression is repressed by the recruitment of NAB proteins (NGFI-A binding protein) 1 and 2 through an interaction with EGR1 at its cognate promoter site, establishing a negative feedback loop (Russo et al, 1993; Russo et al, 1995; Svaren et al, 1996; Kumbrick et al, 2005; Kumbrick et al, 2010). NAB proteins interact with the EGR R1 domain through a conserved NCD1 domain (NAB conserved domain 1) and this interaction is abrogated by mutation of EGR residue I293 (Svaren et al, 1996; Russo, 1993). NCD1 is also required for multimerization of the NAB proteins (Savern et al, 1996; Svaren et al, 1998). Two other conserved regions of NAB proteins (NCD2 and CID, for CHD4-interacting domain) are required for the repression function of the proteins (Svaren et al, 1996; Srinivasan et al, 2006). In some contexts, NAB proteins have also been shown to activate EGR-mediated transcription, and EGR- and NAB-dependent transcription is required for peripheral nervous system myelination (Sevetson et al, 2000; Le et al, 2005).

Literature References
PubMed ID Title Journal Year
10734128 A novel activation function for NAB proteins in EGR-dependent transcription of the luteinizing hormone beta gene

Milbrandt, J, Sevetson, BR, Svaren, J

J. Biol. Chem. 2000
16136673 Nab proteins are essential for peripheral nervous system myelination

Nagarajan, R, Wang, JY, Araki, T, Le, N, Milbrandt, J, Svaren, J, LaPash, C, Schmidt, RE

Nat. Neurosci. 2005
16574654 NAB2 represses transcription by interacting with the CHD4 subunit of the nucleosome remodeling and deacetylase (NuRD) complex

Mager, GM, Ward, RM, Mayer, J, Svaren, J, Srinivasan, R

J. Biol. Chem. 2006
8668170 NAB2, a corepressor of NGFI-A (Egr-1) and Krox20, is induced by proliferative and differentiative stimuli

Popescu, NC, Zimonjic, DB, Milbrandt, J, Apel, ED, Sevetson, BR, Svaren, J

Mol. Cell. Biol. 1996
8413279 Transcriptional activity of the zinc finger protein NGFI-A is influenced by its interaction with a cellular factor

Russo, MW, Milbrandt, J, Matheny, C

Mol. Cell. Biol. 1993
16260776 Egr-1 induces the expression of its corepressor nab2 by activation of the nab2 promoter thereby establishing a negative feedback loop

Gerlinger, M, Johnson, JP, Kumbrink, J

J. Biol. Chem. 2005
7624335 Identification of NAB1, a repressor of NGFI-A- and Krox20-mediated transcription

Russo, MW, Milbrandt, J, Sevetson, BR

Proc. Natl. Acad. Sci. U.S.A. 1995
9774344 Novel mutants of NAB corepressors enhance activation by Egr transactivators

Swirnoff, AH, Milbrandt, J, Sevetson, BR, Svaren, J, Stanton, JJ, Golda, T

EMBO J. 1998
20506119 EGR1, EGR2, and EGR3 activate the expression of their coregulator NAB2 establishing a negative feedback loop in cells of neuroectodermal and epithelial origin

Johnson, JP, Kumbrink, J, Kirsch, KH

J. Cell. Biochem. 2010
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