Regulation of histone acetylation and nucleosome assembly by transcription factor JDP2

Abstract

Jun dimerization protein-2 (JDP2) is a component of the AP-1 transcription factor that represses transactivation mediated by the Jun family of proteins. Here, we examine the functional mechanisms of JDP2 and show that it can inhibit p300-mediated acetylation of core histones in vitro and in vivo. Inhibition of histone acetylation requires the N-terminal 35 residues and the DNA-binding region of JDP2. In addition, we demonstrate that JDP2 has histone-chaperone activity in vitro. These results suggest that the sequence-specific DNA-binding protein JDP2 may control transcription via direct regulation of the modification of histones and the assembly of chromatin.

JDP2 suppresses adipocyte differentiation by regulating histone acetylation

“…We and others reported that JDP2 is an AP-1 transcriptional repressor 15,[17][18][19][20] with histone-chaperone activity that inhibits histone acetylation by recruiting HDAC3. 24 JDP2 also inhibited the RA-dependent differentiation of embryonic carcinoma F9 cells. 18 These findings were obtained from the studies in vitro and the overexpression studies in vivo.…”

“…18 Moreover, we showed also that JDP2 can act directly to inhibit the histone acetyltransferase (HAT) activity induced by p300 in undifferentiated F9 cells and that it induces chromatin assembly. 24 In the presence of RA, JDP2 and HDAC3 were excluded from the differentiation response element (DRE) site and p300 HAT was recruited to this site during the RA-induced differentiation of F9 cells. Therefore, we next examined the involvement of HDAC3 and p300 in adipocyte differentiation.…”

“…We demonstrated recently that JDP2 has histone-chaperone activity and participates in nucleosome assembly in vitro. 24 The molecular network of JDP2 between the chromatin modification and the regulation of proliferation, differentiation and apoptosis of cells still remains to be solved.…”

IRF2‐binding protein‐1 is a JDP2 ubiquitin ligase and an inhibitor of ATF2‐dependent transcription

“…It mediates the differentiation of myoblasts [5] and osteoclasts [6], inhibits the differentiation of adipocytes [7] and embryonic carcinoma cells [8], acts as a tumor suppressor in NIH3T3 cells and prostate cancer cell lines [9], induces the partial transformation of chick embryonic fibroblasts [10], and functions as a cell-survival protein [11] and as a progesterone receptor coactivator [12]. The mechanisms of JDP2-mediated transcriptional repression may include the regulation of nucleosome assembly and histone acetylation [13]. These diverse functions of JDP2 suggest that it cooperates with various proteins to mediate regulatory activity.…”

Promoter Region-Specific Histone Incorporation by the Novel Histone Chaperone ANP32B and DNA-Binding Factor KLF5

“…), and ATPdependent nucleosome remodeling factors (4,22,25,41,46). Recent studies have further suggested that the histone chaperones are important key regulators of chromatin/nucleosome structural regulation in many if not all higher-order DNAassociated processes ranging from transcription to DNA replication/repair (1,2,8,12,16,23,35,38,50). Of these three classes of chromatin/nucleosome-modulating factors, the mechanisms and actions of the histone chaperones, which are the central regulators of nucleosome assembly/disassembly (histone incorporation/eviction) (4,5,17,52), are the least well understood.…”