Chromatin Remodeling by SWI/SNF Results in Nucleosome Mobilization to Preferential Positions in the Rat Osteocalcin Gene Promoter

Abstract

Changes in local chromatin structure accompany transcriptional activation of eukaryotic genes. In vivo these changes in chromatin organization can be catalyzed by ATP-dependent chromatin-remodeling complexes, such as SWI/SNF. These complexes alter the tight wrapping of DNA in the nucleosomes and can facilitate the mobilization of the histone octamer to adjacent DNA segments, leaving promoter regulatory elements exposed for transcription factor binding. To gain understanding of how the activity of SWI/SNF complexes may be modulated by the different DNA sequences within a natural promoter, we have reconstituted nucleosomes containing promoter segments of the transcriptionally active cell type-specific osteocalcin (OC) gene and determined how they affect the directional movements of the nucleosomes. Our results indicate that SWI/SNF complexes induce octamer sliding to preferential positions in the OC promoter, leading to a nucleosomal organization that resembles that described in intact cells expressing the OC gene. Our studies demonstrate that the position of the histone octamer is primarily determined by sequences within the OC promoter that include or exclude nucleosomes. We propose that these sequences are critical components of the regulatory mechanisms that mediate expression of this tissue-specific gene.

Calcitonin, a Regulator of the 25-Hydroxyvitamin D3 1α-Hydroxylase Gene

“…ing with transcription factors such as Myb and CBP/P300 (43,44,57,58). C/EBP␤ also possesses the capacity to suppress gene expression directly through its repression domains or indirectly through other co-factors.…”

Control of Nucleosome Positions by DNA Sequence and Remodeling Machines

“…[70,84,85]). In addition, human SWI/SNF was shown to move histones part way off the edge of some DNA sequences but not others [68].…”

Regulation of nucleosome landscape and transcription factor targeting at tissue-specific enhancers by BRG1

“…The mammalian ATP-dependent chromatin-remodeling BAF complexes (Wang et al 1996) are capable of altering histone-DNA interactions and sliding nucleosomes in vitro (Imbalzano et al 1994;Gutierrez et al 2007), as well as regulating the expression of numerous genes in vivo (Liu et al 2001;Fan et al 2005;Ho et al 2009). BRG1 is involved in numerous cellular differentiation programs including T cell, erythrocyte, and neuronal lineages (Zhao et al 1998;Bultman et al 2000;Chi et al 2002;Im et al 2005;Wu et al 2007;Jani et al 2008;Wurster and Pazin 2008;Kim et al 2009b).…”