Topological regulation of the estrogen transcriptional response by ZATT-mediated inhibition of TOP2B activity.

Human type-II topoisomerases, TOP2A and TOP2B, remove transcription associated DNA supercoiling, thereby affecting gene-expression programs, and have recently been associated with 3D genome architecture. Here, we study the regulatory roles of TOP2 paralogs in response to estrogen, which triggers an acute transcriptional induction that involves rewiring of genome organization. We find that, whereas TOP2A facilitates transcription, as expected for a topoisomerase, TOP2B limits the estrogen response. Consistent with this, TOP2B activity is locally downregulated upon estrogen treatment to favor the establishment and stabilization of regulatory chromatin contacts, likely through an accumulation of DNA supercoiling. We show that estrogen-mediated inhibition of TOP2B requires estrogen receptor α (ERα), a non-catalytic function of TOP2A, and the action of the atypical SUMO-ligase ZATT. This mechanism of topological transcriptional-control, which may be shared by additional gene-expression circuits, highlights the relevance of DNA topoisomerases as central actors of genome dynamics.

Manifestaciones mucocutáneas del Síndrome de Cowden. Presentación de un caso clínico / Mucocutaneous manifestations of the Cowden Syndrome. Presentation of a clinical case

El síndrome de Cowden es una rara enfermedad hereditaria autosómica dominante que se caracteriza por la presencia de múltiples lesiones mucocutáneas de aparición precoz y por la existencia de hamartomas en múltiples localizaciones del organismo entre las que destacan preferentemente intestino, mama y tiroides. La importancia de este síndrome reside en el alto grado de malignización de los tumores que aparecen sobre todo localizados en mama y tiroides. El odontólogo debe ser capaz de diagnosticarlo precozmente a través de las lesiones orales que se dan desde edades muy tempranas en los individuos que lo padecen y que pueden ser motivo de consulta por parte de éstos. Se presenta un caso clínico en el cual el paciente no fue diagnosticado hasta los 38 años de edad de esta afectación sindrómica pero cuyas alteraciones mucocutáneas comenzaron años atrás (AU)

The Cowden Syndrome is an autosomal dominan thereditary rare disease that is characterized by the presence of multiple mucocutaneous lesions of early appearance and by the existence of hamartomas in multiple locations of the body among which stand out preferentially the intestine, breast and thyroid. The importance of this syndrome resides in the high degree of malignization of the tumours that appear especially in the breast and thyroid. The dentist must be capable of diagnosing it early through the oral lesions that occur from very early ages in the individuals that suffer it and that can be a reason for consultation by them. A clinical case is presented in which the patient with this syndromic affectation was not diagnosed until 38 years of age but whose mucocutaneous alterations beganyears before (AU)