A new role for STAT3 as a regulator of chromatin topology

Abstract

The spatial organization of the genome is known to be important for regulation of gene transcription during normal development and in disease states. However, molecular mechanisms governing structural rearrangements in the genome are still poorly understood. Recently, a role for transcription factors in reorganization of the three-dimensional genome structure has been suggested. Distribution of Signal Transducer and Activator of Transcription (STAT) binding sites on genomic DNA and the ability of this family of transcription factors to form phosphorylated (P-STAT) tetramers and unphosphorylated (U-STAT) dimers suggest that some family members, particularly STAT3, may be directly involved in regulation of chromatin topology. The hypothesis is supported by observations of binding of P-STAT3 dimers to adjacent sites on DNA and ability of U- STAT3 to bend and loop DNA. Here we discuss potential roles for STAT3 and other STAT family members in the regulation of gene expression by modulation of chromatin organization.

Keywords: :

• phosphorylated STAT3
• unphosphorylated STAT3
• N-domain
• chromatin organization
• DNA binding
• DNA bending and looping

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

This research was supported in part by American Cancer Society Grant IRG 97–152–17 (OT); NSF grant 0941228 and GW CCFF award (YZ and CZ); the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research (NT); and National Cancer Institute Award P30CA051008.