Evaluation of genome-wide chromatin library of Stat5 binding sites in human breast cancer

BACKGROUND: There is considerable interest in identifying target genes and chromatin binding sites for transcription factors in a genome-wide manner. Such information may become useful in diagnosis and treatment of disease, drug target identification, and for prognostication. In cancer diagnosis, patterns of transcription factor binding to specific regulatory chromatin elements are expected to complement and enhance current diagnostic predictions of tumor behavior based on protein and mRNA analyses. Signal transducer and activator of transcription-5 (Stat5) is a cytokine-activated transcription factor implicated in growth and progression of many malignancies, including hematopoietic, prostate, and breast cancer. We have explored immunoaffinity purification of Stat5-bound chromatin from breast cancer cells to identify Stat5 target sites in an unbiased, genome-wide manner. RESULTS: In this report, we evaluate the efficacy of a Stat5-bound chromatin library to identify valid Stat5 chromatin binding sites within the oncogenome of T-47D human breast cancer cells. A general problem with cloning of immunocaptured, transcription factor-bound chromatin fragments is contamination with non-specific chromatin. However, using an optimized strategy, five out of ten randomly selected clones could be experimentally verified to bind Stat5 both in vitro and in vivo as tested by electrophoretic mobility shift assay and chromatin immunoprecipitation, respectively. While there was no binding to fragments lacking a Stat5 consensus binding sequence, presence of a Stat5 binding sequence did not assure binding. CONCLUSION: A chromatin library coupled with experimental validation may productively identify novel in vivo Stat5 chromatin binding sites in cancer, including abnormal regulatory sites in tumor-specific neochromatin

Topological protection, disorder, and interactions: Survival at the surface of 3D topological superconductors

We consider the interplay of disorder and interactions upon the gapless surface states of 3D topological superconductors. The combination of topology and superconducting order inverts the action of time-reversal symmetry, so that extrinsic time-reversal invariant surface perturbations appear only as "pseudomagnetic" fields (abelian and non-abelian vector potentials, which couple to spin and valley currents). The main effect of disorder is to induce multifractal scaling in surface state wavefunctions. These critically delocalized, yet strongly inhomogeneous states renormalize interaction matrix elements relative to the clean system. We compute the enhancement or suppression of interaction scaling dimensions due to the disorder exactly, using conformal field theory. We determine the conditions under which interactions remain irrelevant in the presence of disorder for symmetry classes AIII and DIII. In the limit of large topological winding numbers (many surface valleys), we show that the effective field theory takes the form of a Finkel'stein non-linear sigma model, augmented by the Wess-Zumino-Novikov-Witten term. The sigma model incorporates interaction effects to all orders, and provides a framework for a controlled perturbative expansion; the inverse spin or thermal conductance is the small parameter. For class DIII we show that interactions are always irrelevant, while in class AIII there is a finite window of stability, controlled by the disorder. Outside of this window we identify new interaction-stabilized fixed points.Comment: 27 pages, 10 figures. v2: published versio

Melham's Conjecture on Odd Power Sums of Fibonacci Numbers

Ozeki and Prodinger showed that the odd power sum of the first several consecutive Fibonacci numbers of even order is equal to a polynomial evaluated at certain Fibonacci number of odd order. We prove that this polynomial and its derivative both vanish at $1$, and will be an integer polynomial after multiplying it by a product of the first consecutive Lucas numbers of odd order. This presents an affirmative answer to a conjecture of Melham.Comment: 15page