HMG17 is a chromatin-specific transcriptional coactivator that increases the efficiency of transcription initiation.

Abstract

We have examined the effect of HMG17 on transcription by RNA polymerase II by the assembly and analysis of HMG17-containing chromatin templates consisting of regularly spaced nucleosomal arrays. Structural analysis of the chromatin indicated that HMG17 is incorporated into chromatin in a physiological manner with the full complement of core histones. The transcriptional studies revealed that HMG17 stimulates transcription in conjunction with the sequence-specific activator GAL4-VP16. This effect was observed with chromatin, but not with non-nucleosomal templates, and required the presence of HMG17 during chromatin assembly. The incorporation of HMG17 into chromatin resulted in a 7-to 40-fold stimulation of GAL4-VP16-activated transcription to levels that were comparable to those observed with histone-free DNA templates. In contrast, transcription from HMG17-containing chromatin was not detectable in the absence of GAL4--VP16 or with a GAL4 derivative [GAL4(1-147)] lacking the VP16 activation domain. Finally, the incorporation of HMG17 into chromatin was found to increase the efficiency of transcription initiation, but not the extent of transcriptional elongation. Thus, HMG17 is a chromatin-specific transcriptional coactivator that increases the efficiency of initiation of transcription by RNA polymerase II.

cAMP-response Element-binding Protein (CREB) Controls MSK1-mediated Phosphorylation of Histone H3 at the c-fos Promoter in Vitro

“…S3B). Consistent with the previous study (30), the purified HMGN1 could be incorporated efficiently into the chromatin and increased the interval between nucleosomes (Fig. 4A, arrows), an effect that is consistent with its role in chromatin decompaction.…”

“…An SDS-PAGE analysis revealed that the precipitated chromatin contained roughly equivalent moles of HMGN1 and core histones (Fig. 4C), consistent with the incorporation of two HMGN1 molecules per each nucleosome (30,31).…”

Increased Tumorigenicity and Sensitivity to Ionizing Radiation upon Loss of Chromosomal Protein HMGN1

“…The growth control mechanisms disrupted by loss of HMGN1 protein may have rendered the animals and the MEFs more susceptible to additional events that ultimately lead to malignant transformations. The interaction of HMGN1 protein with nucleosomes alters the structure of chromatin and modulates various DNA-related nuclear processes including transcription (18)(19)(20). Thus, the increased tumor burden and tumorigenicity of Hmgn1 À/À mice and MEFs could be due not only to an impaired G 2 -M checkpoint but also to indirect effects that lead to alteration in the cellular transcription profile.…”

“…HMGN proteins move rapidly throughout the nucleus, bind to nucleosomes transiently (16,17), and reduce the compaction of the chromatin fiber (14,15). The binding of HMGN proteins to nucleosomes affects the levels of posttranslational modification in core histones and alters DNArelated nuclear processes such as transcription (18)(19)(20) and replication (21). Hmgn1 À/À mice are hypersensitive to UV most likely because loss of HMGN1 protein alters the accessibility of the damaged sites to the nucleotide excision repair machinery and decreases the rate of removal of UV-induced lesions from transcriptionally active chromatin (22).…”

p300 and estrogen receptor cooperatively activate transcription via differential enhancement of initiation and reinitiation

“…Also, in the initial experiments (Figs. 2 and 3), chromatin was assembled in the presence of HMG-17 (10 molecules/180 bp of specific template DNA) (Paranjape et al 1995). When added at this amount, the HMG-17 increased the E 2 -dependent activity of the ER with the chromatin templates by a factor of ∼1.5-2.…”