Distinct Mechanisms Control RNA Polymerase II Recruitment to a Tissue-Specific Locus Control Region and a Downstream Promoter

ABSTRACT The human serine protease inhibitor (serpin) gene cluster at 14q32.1 comprises 11 serpin genes, many of which are expressed specifically in hepatic cells. Previous studies identified a locus control region (LCR) upstream of the human α1-antitrypsin (α1AT) gene that is required for gene activation, chromatin remodeling, and histone acetylation throughout the proximal serpin subcluster. Here we show that the LCR interacts with multiple liver-specific transcription factors, including hepatocyte nuclear factor 3β (HNF-3β), HNF-6α, CCAAT/enhancer binding protein alpha (C/EBPα), and C/EBPβ. RNA polymerase II is also recruited to the locus through the LCR. Nongenic transcription at both the LCR and an upstream regulatory region was detected, but the deletion of the LCR abolished transcription at both sites. The deletion of HNF-3 and HNF-6 binding sites within the LCR reduced histone acetylation at both the LCR and the upstream regulatory region and decreased the transcription of the α1AT, corticosteroid binding globulin, and protein Z-dependent protease inhibitor genes. These results suggest that the LCR activates genes in the proximal serpin subcluster by recruiting liver-specific transcription factors and components of the general transcription machinery to regulatory regions upstream of the α1AT gene.

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Highly Restricted Localization of RNA Polymerase II within a Locus Control Region of a Tissue-Specific Chromatin Domain

Molecular and Cellular Biology ◽

10.1128/mcb.23.18.6484-6493.2003 ◽

2003 ◽

Vol 23 (18) ◽

pp. 6484-6493 ◽

Cited By ~ 66

Author(s):

Kirby D. Johnson ◽

Jeffrey A. Grass ◽

Changwon Park ◽

Hogune Im ◽

Kyunghee Choi ◽

...

Keyword(s):

Rna Polymerase ◽

Histone Modification ◽

Rna Polymerase Ii ◽

Control Region ◽

Locus Control Region ◽

Regulatory Elements ◽

Chromatin Domain ◽

Pol Ii ◽

Reading Frame ◽

Hypersensitive Sites

ABSTRACT RNA polymerase II (Pol II) can associate with regulatory elements far from promoters. For the murine β-globin locus, Pol II binds the β-globin locus control region (LCR) far upstream of the β-globin promoters, independent of recruitment to and activation of the βmajor promoter. We describe here an analysis of where Pol II resides within the LCR, how it is recruited to the LCR, and the functional consequences of recruitment. High-resolution analysis of the distribution of Pol II revealed that Pol II binding within the LCR is restricted to the hypersensitive sites. Blocking elongation eliminated the synthesis of genic and extragenic transcripts and eliminated Pol II from the βmajor open reading frame. However, the elongation blockade did not redistribute Pol II at the hypersensitive sites, suggesting that Pol II is recruited to these sites. The distribution of Pol II did not strictly correlate with the distributions of histone acetylation and methylation. As Pol II associates with histone-modifying enzymes, Pol II tracking might be critical for establishing and maintaining broad histone modification patterns. However, blocking elongation did not disrupt the histone modification pattern of the β-globin locus, indicating that Pol II tracking is not required to maintain the pattern.

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Study of the novel tissue-specific RNA polymerase II transcription factor

Russian Journal of Genetics ◽

10.1007/s11177-005-0105-x ◽

2005 ◽

Vol 41 (4) ◽

pp. 425-429 ◽

Cited By ~ 1

Author(s):

P. V. Mardanov ◽

A. N. Krasnov ◽

M. M. Kurshakova ◽

E. N. Nabirochkina ◽

S. G. Georgieva

Keyword(s):

Transcription Factor ◽

Rna Polymerase ◽

Rna Polymerase Ii ◽

The Novel ◽

Tissue Specific ◽

Rna Polymerase Ii Transcription

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Antagonistic Regulation of β-Globin Gene Expression by Helix-Loop-Helix Proteins USF and TFII-I

Molecular and Cellular Biology ◽

10.1128/mcb.01770-05 ◽

2006 ◽

Vol 26 (18) ◽

pp. 6832-6843 ◽

Cited By ~ 30

Author(s):

Valerie J. Crusselle-Davis ◽

Karen F. Vieira ◽

Zhuo Zhou ◽

Archana Anantharaman ◽

Jörg Bungert

Keyword(s):

Gene Expression ◽

Rna Polymerase Ii ◽

Control Region ◽

Adult Stage ◽

Globin Gene ◽

Locus Control Region ◽

Erythroid Cell ◽

Erythroid Cells ◽

Globin Gene Expression ◽

In Erythroid Cells

ABSTRACT The human β-globin genes are expressed in a developmental stage-specific manner in erythroid cells. Gene-proximal cis-regulatory DNA elements and interacting proteins restrict the expression of the genes to the embryonic, fetal, or adult stage of erythropoiesis. In addition, the relative order of the genes with respect to the locus control region contributes to the temporal regulation of the genes. We have previously shown that transcription factors TFII-I and USF interact with the β-globin promoter in erythroid cells. Herein we demonstrate that reducing the activity of USF decreased β-globin gene expression, while diminishing TFII-I activity increased β-globin gene expression in erythroid cell lines. Furthermore, a reduction of USF activity resulted in a significant decrease in acetylated H3, RNA polymerase II, and cofactor recruitment to the locus control region and to the adult β-globin gene. The data suggest that TFII-I and USF regulate chromatin structure accessibility and recruitment of transcription complexes in the β-globin gene locus and play important roles in restricting β-globin gene expression to the adult stage of erythropoiesis.

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