A Thymocyte Factor SATB1 Suppresses Transcription of Stably Integrated Matrix-Attachment Region-Linked Reporter Genes

Abstract

SATB1 specifically recognizes and binds to specialized genomic regions with an ATC sequence context with high base-unpairing propensity. Such base-unpairing regions (BURs) are typically identified within nuclear scaffold- or matrix-attachment regions (S/MARs). SATB1 is a homeodomain protein and is predominantly expressed in thymocytes. We obtained BHK cell lines expressing low levels of SATB1 by stable transfection and investigated its effect on stably integrated MAR-linked SV40 enhancer/promoter-driven luciferase reporter genes. For this study, both naturally occurring and synthetic MARs, as well as an AT-rich non-MAR control, were tested. Previous studies demonstrated that MAR sequences augment transcription of the linked reporter luciferase gene. Here, we show that SATB1 dramatically reduces the high levels of MAR-linked luciferase gene transcription. Transcription was virtually abolished for a reporter gene surrounded by two MARs at the 5' and 3' ends of the gene, which otherwise confer the highest level of transcriptional augmentation. On the other hand, SATB1 did not affect expression of an AT-rich non-MAR-linked luciferase gene or of endogenous housekeeping genes. This study shows that SATB1 acts as a strong transcriptional suppressor on a reporter gene linked to MARs when it is stably integrated into chromatin.

A distal single nucleotide polymorphism alters long-range regulation of the PU.1 gene in acute myeloid leukemia

“…The highly conserved PU.1-regulating URE is located 16 kb (human) and 14 kb (murine), upstream of the transcriptional start site of PU.1, suggesting that SATB1 has a similar long-range mechanism in myeloid cells. Several reports have shown a transcription-repressing function of SATB1 in T cells (26,27). Recently, Wen et al have shown that SATB1 positively regulates e-globin gene expression in erythroid progenitor cells (28).…”

Abnormal V(D)J Recombination of T Cell Receptor β Locus in SMAR1 Transgenic Mice

“…SATB1 is a more T cell-specific protein; Bright being specific for B cells whereas Cux exhibits ubiquitous expression. Cux and SATB1 have been known to function as strong transcriptional repressors (30,31) whereas Bright functions as a transcriptional activator (44). Both Cux and SATB1 proteins play significant role in various processes such as chromatin remodeling, tissuespecific gene regulation, and cell cycle progression, specifying cell fates during cell development and differentiation as well as tumor-specific metabolism (45)(46)(47)(48).…”

“…MARs help the cell type-specific expression of genes by residing close to enhancers as well as by synergistically acting with them (29), thus maintaining some chromatin domains in condensed inactive structures and others in decondensed transcriptionally active structures. MARs flanking the enhancers in the immunoglobulin or T cell receptor genes are known to function in association with their specific MAR-binding proteins such as Cux (30) and SATB1 (31). Earlier, we reported a novel MAR-binding protein, SMAR1, interacting with MAR␤ (32), a MAR flanking 5Ј-end of the TCR␤ enhancer (E␤) (33).…”

Matrin 3 Augments the Transcriptional Activity of an SV40 Promoter-Mediated Luciferase Gene with a Highly Repetitive DNA Component

“…SATB1 regulates transcription activity and recruits chromatin-remodeling factors for region-specific histone modification [12][13][14][15][16], SATB2 activates gamma-globin genes by binding to MARs in their promoters and recruiting histone acetylase PCAF [17]. SAF-B suppresses transcription activity through a recombinant promoter constructs resembling the lysozyme 5` MAR promoter [18].…”