Differential sensitivities of transcription factor target genes underlie cell type-specific gene expression profiles.

Differential sensitivities of transcription factor target genes underlie cell type-specific gene expression profiles. Research Abstract Details 

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Differential sensitivities of transcription factor target genes underlie cell type-specific gene expression profiles. Abstract Text:

Kirby D Johnson,Shin-Il Kim,Emery H Bresnick,

Changes in transcription factor levels and activities dictate developmental fate. Such a change might affect the full ensemble of target genes for a factor or only uniquely sensitive targets. We investigated the relationship among activity of the hematopoietic transcription factor GATA-1, chromatin occupancy, and target gene sensitivity. Graded activation of GATA-1 in GATA-1-null cells revealed high-, intermediate-, and low-sensitivity targets. GATA-1 activity requirements for occupancy and transcription often correlated. A GATA-1 amino-terminal deletion mutant severely deregulated the low-sensitivity gene Tac-2. Thus, cells expressing different levels of a cell type-specific activator can have qualitatively distinct target gene expression patterns, and factor mutations preferentially deregulate low-sensitivity genes. Unlike other target genes, GATA-1-mediated Tac-2 regulation was bimodal, with activation followed by repression, and the coregulator Friend of GATA-1 (FOG-1) selectively mediated repression. A GATA-1 mutant defective in FOG-1 binding occupied a Tac-2 regulatory region at levels higher than wild-type GATA-1, whereas FOG-1 facilitated chromatin occupancy at a distinct target site. These results indicate that FOG-1 is a determinant of GATA factor target gene sensitivity by either facilitating or opposing chromatin occupancy.

Differential sensitivities of transcription factor target genes underlie cell type-specific gene expression profiles. Publishing Authors By Initials

KD Johnson,SI Kim,EH Bresnick,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: protein binding research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: protein binding research

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Differential sensitivities of transcription factor target genes underlie cell type-specific gene expression profiles. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 103

Page Numbers: 15939-44

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 16

MONTH: 10

YEAR: 2006

Differential sensitivities of transcription factor target genes underlie cell type-specific gene expression profiles. Information

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LANGUAGE: eng

NlmUniqueID: 7505876

Differential sensitivities of transcription factor target genes underlie cell type-specific gene expression profiles. Keywords Mesh Terms:

KEYWORDS: Protein Binding

MESH TERMS: genetics

Chemical & Substance for Abstract: Differential sensitivities of transcription factor target genes underlie cell type-specific gene expression profiles. Information

Substance Name: Neurokinin B

Registry Number: 86933-75-7

Grant and Affiliation Information for Differential sensitivities of transcription factor target genes underlie cell type-specific gene expression profiles.

AFFILIATION: Molecular and Cellular Pharmacology Program, Department of Pharmacology, University of Wisconsin School of Medicine, 383 Medical Sciences Center, 1300 University Avenue, Madison, WI 53706, USA.

Country: United States

AGENCY: United States PHS

GRANT: T32NL07899

ACRONYM: DK

MEDLINETA: Proc Natl Acad Sci U S A

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