MXD/MIZ1 transcription regulatory complexes activate the expression of MYC‐repressed genes

Abstract

MXDs are transcription repressors that antagonize MYC-mediated gene activation. MYC, when associated with MIZ1, acts also as a repressor of a subset of genes, including p15 and p21. A role for MXDs in regulation of MYCrepressed genes is not known. We report that MXDs activate transcription of p15 and p21 in U2OS cells. This activation required DNA binding by MXDs and their interaction with MIZ1. MXD mutants deficient in MIZ1 binding interacted with the MYC-binding partner MAX and were active as repressors of MYC-activated genes but failed to activate MYC-repressed genes. Mutant MXDs with reduced DNA-binding affinity interacted with MAX and MIZ1 but neither repressed nor activated transcription. Our data show that MXDs and MYC have a reciprocally antagonistic potential to regulate transcription of target genes.

Neurospora casein kinase 1a recruits the circadian clock protein FRQvia the C‐terminal lobe of its kinase domain

“…The membranes were washed three times with TBS for 10 min and incubated with secondary antibody for 2 h at RT [goat antimouse IgG (H + L)-HRP conjugate, Bio-Rad (170-6516), for decoration of FRQ and FLAG; or goat anti-rabbit IgG (H + L)-HRP conjugate, Bio-Rad (172-1019), for WC-2 and CK1a]. Membranes were incubated with luminol and exposed to X-ray films (Fujifilm, medical film processor from Konica Minolta) as described [7,35].…”

“…(A) Race tube analysis [45] showing that ck1a-p1 does not support the circadian conidiation rhythm of Neurospora. (B) Bioluminescence recordings [35,46] of wt and ck1a-p1 strains expressing a frq-lucPEST reporter gene. Traces are averages of eight technical replicates.…”

Transcription activator WCC recruits deacetylase HDA3 to control transcription dynamics and bursting in Neurospora

“…Activation and repression could be mediated by the same TF, as shown here for the WCC. In other cases, transcription dynamics are regulated by TF-families of activators and repressors binding to the same regulatory elements, such as MYCs and MXDs or Rev/ERBs and RORs (44)(45)(46)(47)(48)(49) or by the combinatorial activity of unrelated regulators.…”

Transcription activator WCC recruits deacetylase HDA3 to control transcription dynamics and bursting in Neurospora

“…Activation and repression could be mediated by the same TF, as shown here for the WCC. In other cases, transcription dynamics are regulated by TF families of activators and repressors binding to the same regulatory elements, such as MYC proteins and MAX dimerizations (MXDs) or nuclear receptor subfamily 1 group D (Rev/ERBs) and retinoic acid-related orphan receptors (RORs) (44)(45)(46)(47)(48)(49), or by the combinatorial activity of unrelated regulators.…”