SAR-dependent mobilization of histone H1 by HMG-I/Y in vitro: HMG-I/Y is enriched in H1-depleted chromatin.

Abstract

An experimental assay was developed to search for proteins capable of antagonizing histone H1‐mediated general repression of transcription. T7 RNA polymerase templates containing an upstream scaffold‐associated region (SAR) were highly selectively repressed by H1 relative to non‐SAR control templates. This is due to the nucleation of H1 assembly into flanking DNA brought about by the numerous A‐tracts (AT‐rich sequences containing short homopolymeric runs of dA.dT base pairs) of the SAR. Partial, selective titration of these A‐tracts by the high mobility group (HMG) protein HMG‐I/Y led to the complete derepression of transcription from the SAR template by inducing the redistribution of H1 on to non‐SAR templates. SARs are associated with many highly transcribed regulated genes where they may serve to facilitate the HMG‐I/Y‐mediated displacement of histone H1 in chromatin. Indeed, HMG‐I/Y was found to be strongly enriched in the H1‐depleted subfraction which can be isolated from chromatin.

TGF-β and IL-6 signals modulate chromatin binding and promoter occupancy by acetylated FOXP3

“…We examined the distribution patterns of FOXP3 in discrete subnuclear compartments after T cell stimulation. A full-length FOXP3 expression construct, pIPHA2FOXP3a, was transiently expressed in Jurkat T cells (5,8), and cell constituents were separated into nuclear and chromatin fractions based on defined protocols (28,29). We noted small amounts of full-length FOXP3a in the cytoplasm (Fig.…”

Specific Binding of High-Mobility-Group I (HMGI) Protein and Histone H1 to the Upstream AT-Rich Region of the Murine Beta Interferon Promoter: HMGI Protein Acts as a Potential Antirepressor of the Promoter

“…For the binding of histone H1 to SAR, it was shown that HMGI protein can compete with histone H1 for binding to these AT-rich DNA sequences, displace histone H1, and derepress a T7 promoter (49). Upstream binding factor 3 has also been described as capable of displacing histone H1.…”

A retrospective study of high mobility group protein I(Y) as progression marker for prostate cancer determined by in situ hybridization

“…Thus, there seems to be a trend towards higher HMG-I(Y) levels in higher stage tumours, which might be a HMG-I(Y) has been implicated in a number of functions: the subunits of NF-KB (p50 and p65), members of the oncogene rel family, can only activate transcription from their binding site PRDII when HMG-I(Y) is also bound (Thanos et al, 1992), similarly the E-selectin gene, encoding for endothelial cell adhesion proteins, can be activated only via interleukin (IL)-13 and tumour necrosis factor (TNF)-cx induction of NF-KB through HMG-I(Y) binding (Lewis et al, 1994). HMG-I(Y) is involved in rescuing scaffoldassociated regions (SARs) and A:T rich sequences from histone HI-mediated repression, which fold the chromatin fibre into higher order structures (Zhao et al, 1993); finally HMG-I(Y) plays a role in the suppression of IL-4 transcription in T lymphocytes (Chuvpilo et al, 1993), as well as in the stimulation of a specific isoform of the activating transcription factor 2 (ATF-2195) binding to interferon ,B (IFN-fl) (Du et al, 1994). In view of the multifunctionality of HMG-I(Y) in mammalian cells, it is not Correlation between stage and HMG-I(Y) expression over and below a threshold of 0.65 (normalised score A).…”