Quantitative signature for architectural organization of regulatory factors using intranuclear informatics.
Regulatory machinery for replication and gene expression is punctately organized in supramolecular complexes that are compartmentalized in nuclear microenvironments. Quantitative approaches are required to understand the assembly of regulatory machinery within the context of nuclear architecture and to provide a mechanistic link with biological control. We have developed 'intranuclear informatics' to quantify functionally relevant parameters of spatially organized nuclear domains. Using this informatics strategy we have characterized post-mitotic reestablishment of focal subnuclear organization of Runx (AML/Cbfa) transcription factors in progeny cells. By analyzing point mutations that abrogate fidelity of Runx intranuclear targeting, we establish molecular determinants for the spatial order of Runx domains. Our novel approach provides evidence that architectural organization of Runx factors may be fundamental to their tissue-specific regulatory function.
Young
Daniel W
DW
Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester 01655-0106, USA.
Zaidi
Sayyed K
SK
Furcinitti
Paul S
PS
Javed
Amjad
A
van Wijnen
Andre J
AJ
Stein
Janet L
JL
Lian
Jane B
JB
Stein
Gary S
GS
D000818:Animals; D001671:Biochemistry / Q000379:methods*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D050657:Core Binding Factor alpha Subunits; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008856:Microscopy, Fluorescence; D008938:Mitosis; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism*; D015530:Nuclear Matrix / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D002843:Chromatin; D050657:Core Binding Factor alpha Subunits; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors