Increased actin polymerization reduces the inhibition of serum response factor activity by Yin Yang 1

Peter D Ellis, Karen M Martin, Colin Rickman, James C Metcalfe, Paul R Kemp

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Recent evidence has implicated CC(A/T(richG))GG (CArG) boxes, binding sites for serum response factor (SRF), in the regulation of expression of a number of genes in response to changes in the actin cytoskeleton. In many cases, the activity of SRF at CArG boxes is modulated by transcription factors binding to overlapping (e.g. Yin Yang 1, YY1) or adjacent (e.g. ets) binding sites. However, the mechanisms by which SRF activity is regulated by the cytoskeleton have not been determined. To investigate these mechanisms, we screened for cells that did or did not increase the activity of a fragment of the promoter for a smooth-muscle (SM)-specific gene SM22alpha, in response to changes in actin cytoskeletal polymerization induced by LIM kinase. These experiments showed that vascular SM cells (VSMCs) and C2C12 cells increased the activity of promoters containing at least one of the SM22alpha CArG boxes (CArG near) in response to LIM kinase, whereas P19 cells did not. Bandshift assays using a probe to CArG near showed that P19 cells lacked detectable YY1 DNA binding to the CArG box in contrast with the other two cell types. Expression of YY1 in P19 cells inhibited SM22alpha promoter activity and conferred responsiveness to LIM kinase. Mutation of the CArG box to inhibit YY1 or SRF binding indicated that both factors were required for the LIM kinase response in VSMCs and C2C12 cells. The data indicate that changes in the actin cytoskeletal organization modify SRF activity at CArG boxes by modulating YY1-dependent inhibition.
Original languageEnglish
Pages (from-to)547-554
Number of pages8
JournalBiochemical Journal
Volume364
Issue number2
DOIs
Publication statusPublished - 1 Jun 2002

Keywords

  • Actins
  • Base Sequence
  • Binding Sites
  • Biopolymers
  • Cell Line
  • DNA Primers
  • DNA-Binding Proteins
  • Depsipeptides
  • Electrophoretic Mobility Shift Assay
  • Erythroid-Specific DNA-Binding Factors
  • Lim Kinases
  • Microfilament Proteins
  • Muscle Proteins
  • Peptides, Cyclic
  • Promoter Regions, Genetic
  • Protein Kinases
  • Serum Response Factor
  • Transcription Factors
  • YY1 Transcription Factor

Fingerprint Dive into the research topics of 'Increased actin polymerization reduces the inhibition of serum response factor activity by Yin Yang 1'. Together they form a unique fingerprint.

  • Cite this