Combinatorial organization of the transcriptional regulatory machinery in biological control and cancer.
The architecturally associated subnuclear organization of nucleic acids and cognate regulatory factors suggests functional interrelationships between nuclear structure and gene expression. Mechanisms that contribute to the spatial distribution of transcription factors within the three dimensional context of nuclear architecture control the sorting and integration of regulatory information as well as the combinatorial assembly, organization and activities of transcriptional machinery at scaffold-associated subnuclear sites that support gene expression. During the past several years our laboratory has been addressing intranuclear trafficking mechanisms that direct transcription factors to transcriptionally active nuclear microenvironments. We are pursuing these studies using the AML/Runx/Cbfa transcription factors that govern hematopoietic and bone-specific transcription as a paradigm. Our objective is to gain insight into linkage of intranuclear organization of genes, transcripts, and regulatory proteins with fidelity of biological control and contributions of aberrant nuclear structure/function relationships to the onset and progression of tumorigenesis.
Stein
Gary S
GS
Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, 55 Lake Ave. North, Worcester, MA 01655, USA. gary.stein@umassmed.edu
Lian
Jane B
JB
Stein
Janet L
JL
van Wijnen
Andre J
AJ
Javed
Amjad
A
Montecino
Martin
M
Zaidi
Sayyed K
SK
Young
Daniel W
DW
Choi
Je-Yong
JY
Pratap
Jitesh
J
D000818:Animals; D002451:Cell Compartmentation / Q000502:physiology; D002467:Cell Nucleus / Q000502:physiology; D050657:Core Binding Factor alpha Subunits / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D015530:Nuclear Matrix / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*
D050657:Core Binding Factor alpha Subunits; D009687:Nuclear Proteins; D014157:Transcription Factors