Inter-MAR association contributes to transcriptionally active looping events in human beta-globin gene cluster

PLoS One. 2009;4(2):e4629. doi: 10.1371/journal.pone.0004629. Epub 2009 Feb 27.

Abstract

Matrix attachment regions (MARs) are important in chromatin organization and gene regulation. Although it is known that there are a number of MAR elements in the beta-globin gene cluster, it is unclear that how these MAR elements are involved in regulating beta-globin genes expression. Here, we report the identification of a new MAR element at the LCR (locus control region) of human beta-globin gene cluster and the detection of the inter-MAR association within the beta-globin gene cluster. Also, we demonstrate that SATB1, a protein factor that has been implicated in the formation of network like higher order chromatin structures at some gene loci, takes part in beta-globin specific inter-MAR association through binding the specific MARs. Knocking down of SATB1 obviously reduces the binding of SATB1 to the MARs and diminishes the frequency of the inter-MAR association. As a result, the ACH establishment and the alpha-like globin genes and beta-like globin genes expressions are affected either. In summary, our results suggest that SATB1 is a regulatory factor of hemoglobin genes, especially the early differentiation genes at least through affecting the higher order chromatin structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Cell Cycle
  • Gene Expression Regulation / physiology
  • Humans
  • K562 Cells
  • Matrix Attachment Region Binding Proteins / genetics
  • Matrix Attachment Region Binding Proteins / physiology
  • Matrix Attachment Regions*
  • Multigene Family*
  • Transcription, Genetic*
  • beta-Globins / genetics*

Substances

  • Matrix Attachment Region Binding Proteins
  • SATB1 protein, human
  • beta-Globins