Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
 Blood, 1 November 2007, Vol. 110, No. 9, pp. 3136-3142.
Prepublished online as a Blood First Edition Paper on August 1, 2007; DOI 10.1182/blood-2007-03-080291.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
blood-2007-03-080291v1
110/9/3136    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yeamans, C.
Right arrow Articles by Friedman, A. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yeamans, C.
Right arrow Articles by Friedman, A. D.
Related Collections
Right arrow Gene Expression
Right arrow Hematopoiesis
Right arrow Phagocytes
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

HEMATOPOIESIS

C/EBP{alpha} binds and activates the PU.1 distal enhancer to induce monocyte lineage commitment

Christine Yeamans1, Dehua Wang1, Ido Paz-Priel1, Bruce E. Torbett2, Daniel G. Tenen3, and Alan D. Friedman1

1 Division of Pediatric Oncology, Johns Hopkins University, Baltimore, MD; 2 The Scripps Research Institute, La Jolla, CA; and 3 Harvard Institute of Medicine, Boston, MA

The PU.1 gene contains a 237–base pair distal enhancer located 14 kilobases upstream of its promoter. We have identified 2 sites within the PU.1 enhancer that strongly bind C/EBP{alpha} in a gel shift assay, and interaction with endogenous C/EBP{alpha} was confirmed by chromatin immunoprecipitation. Mutation of these DNA elements reduced activity of a distal enhancer-promoter construct 2- or 5-fold in a myeloid cell line, while mutation of a weaker C/EBP{alpha}-binding site located in the promoter minimally reduced activity in this context. These findings strengthen the link between C/EBP{alpha} and PU.1 expression. Reduction of C/EBP{alpha} activity in cases of acute myeloid leukemia may therefore contribute to transformation by reducing PU.1 levels. In addition, induction of PU.1 by C/EBP{alpha} during normal hematopoiesis may contribute to stem cell commitment to the myeloid lineages and further commitment to monopoiesis. Consistent with a requirement for C/EBP{alpha} induction of PU.1 during myeloid development, we demonstrate that C/EBP{alpha} induces monocytic development when expressed in PU.1+/+, PU.1+/–, or PU.1+/kd marrow myeloid progenitors but induces granulocyte lineage commitment in PU.1kd/kd cells lacking the PU.1 distal enhancer and does not induce either lineage in PU.1–/– cells.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Mol. Cell. Biol.Home page
M. Hoogenkamp, H. Krysinska, R. Ingram, G. Huang, R. Barlow, D. Clarke, A. Ebralidze, P. Zhang, H. Tagoh, P. N. Cockerill, et al.
The Pu.1 Locus Is Differentially Regulated at the Level of Chromatin Structure and Noncoding Transcription by Alternate Mechanisms at Distinct Developmental Stages of Hematopoiesis
Mol. Cell. Biol., November 1, 2007; 27(21): 7425 - 7438.
[Abstract] [Full Text] [PDF]


click for free articles
home about blood authors subscriptions permissions advertising public access contact us
Sponsor: Genentech BioOncology and and Biogen Idec
Blood Online is supported in part by
Genentech BioOncology and Biogen Idec
  Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020