Histone acetylation and expression of SMN, the spinal muscular atrophy gene

Spinal Muscular Atrophy (SMA) is an inherited neuromuscular disorder caused by mutation of the Survival Motor Neuron (SMN1) gene. Embryonic lethality is rescued by a nearly identical copy of the gene, SMN2, which exists in variable copy number and produces a small quantity of functional SMN protein. Because disease severity inversely correlates with SMN2 gene copy number and with SMN protein level, one therapeutic strategy has been to increase SMN2 expression. Previous investigators have demonstrated that SMN promoter activity, transcript, and SMN protein are increased in cells treated with histone deacetylase (HDAC) inhibitors, suggesting a role for histone acetylation in the regulation of SMN expression. To further investigate epigenetic regulation of SMN, we used chromatin immunoprecipitation to characterize the acetylation state of histones associated with the SMN promoter locus. We show that the SMN promoter has a reproducible pattern of histone acetylation conserved across species and tissues. Following treatment with HDAC inhibitors, we correlated a 2-fold increase in SMN promoter activity, with an increase in H3 and H4 histone acetylation, particularly in upstream regions 2-3 kb from the translational initiation site. During development in mouse tissues, SMN transcript decreased 40-60%, correlating with a decrease in histone acetylation levels within the region closest to the transcriptional start site. These data indicate that histone acetylation is a biologically relevant determinant of SMN gene expression, and that this epigenetic variable can be manipulated pharmacologically

The Distribution Right in the United States of America: Review and Reflections

This Essay on the distribution right considers the possibility and the merits of three options now widely discussed. These are: (a) ex-tending the reach of an old right, the right of reproduction, to include the currently debated droit de destination, or (b) broadening the right of distribution in nations that have such a right by cutting back on the first sale doctrine \u27 and other limitations on that right, and (c) giving authors broad control over use of their work. All of these approaches aim to make authors\u27 rights more substantial and effective to achieve their purpose amid the erosions resulting from technological change. In pursuing this aim we must look carefully at the law and experience of today as evolved from the past. Historic continuity with the past, said Justice Holmes, is not a duty, it is only a necessity. If we are to help develop the law wisely for authors, it also will be necessary to look at the problems, implications, and potentialities of the three options described in a number of specific areas of the arts. Because United States copyright law, in addition to granting a re-production right, expressly provides for a right of distribution, I will begin my review of the United States law and its problems with an examination of that provision. So let me first briefly describe the terms of the United States distribution right and the limitations on it, including the first sale doctrine and other restrictions, as well as some of the existing avenues of expansion or avoidance. It seems best to start by examining the language of the general right currently in force and its history. Such a foundation will anchor and clarify any discussion of the merits and demerits of United States law and put suggestions for change in a sharper perspective

Statutory Interpretation: An Outline of Method

We are moving ever more surely and deeply these days into an age of legislation. In the past, judge-made law was the dominant feature, as it was also the matrix, the fundamental and pervasive stuff, of our legal system. Statutes were scattered islands in the ocean of common law. For some time they were regarded by the courts as peculiar incursions on the system, troubling the harmony of caselaw patterns. A legislative enactment was seen, in the words of the late Chief Justice Stone, as an alien intruder in the house of the common law. But change has come and is currently at work at an astonishing pace. The islands of legislation have become much more numerous; they have become archipelagoes in some areas. The islands have grown in size; some are almost continents. What once seemed a peculiar incursion has become normal and pervasive. Statutes can no longer be regarded as intruders. As more and more common law is displaced, overlaid or supplemented, the system is becoming legislative in character

Statutory Interpretation: An Outline of Method

We are moving ever more surely and deeply these days into an age of legislation. In the past, judge-made law was the dominant feature, as it was also the matrix, the fundamental and pervasive stuff, of our legal system. Statutes were scattered islands in the ocean of common law. For some time they were regarded by the courts as peculiar incursions on the system, troubling the harmony of caselaw patterns. A legislative enactment was seen, in the words of the late Chief Justice Stone, as an alien intruder in the house of the common law. But change has come and is currently at work at an astonishing pace. The islands of legislation have become much more numerous; they have become archipelagoes in some areas. The islands have grown in size; some are almost continents. What once seemed a peculiar incursion has become normal and pervasive. Statutes can no longer be regarded as intruders. As more and more common law is displaced, overlaid or supplemented, the system is becoming legislative in character

Statutory Interpretation: An Outline of Method

We are moving ever more surely and deeply these days into an age of legislation. In the past, judge-made law was the dominant feature, as it was also the matrix, the fundamental and pervasive stuff, of our legal system. Statutes were scattered islands in the ocean of common law. For some time they were regarded by the courts as peculiar incursions on the system, troubling the harmony of caselaw patterns. A legislative enactment was seen, in the words of the late Chief Justice Stone, as an alien intruder in the house of the common law. But change has come and is currently at work at an astonishing pace. The islands of legislation have become much more numerous; they have become archipelagoes in some areas. The islands have grown in size; some are almost continents. What once seemed a peculiar incursion has become normal and pervasive. Statutes can no longer be regarded as intruders. As more and more common law is displaced, overlaid or supplemented, the system is becoming legislative in character

One Hundred and Two Years Later: The U.S. Joins the Berne Convention

In historic votes on October 5 and October 12, the U.S. Senate and House of Representatives unanimously approved legislation designed to bring U.S. law into compliance with the Berne Convention. The legislation was signed by President Reagan on October 31, 1988. Also signed by the President was a Senate Resolution of October 20 of Ratification of the Berne Convention. Following deposit of the requisite instruments with the World Intellectual Property Organization in Geneva, U.S. adherence to Berne took effect on March 1, 1989. For the U.S., this momentous step is the culmination of decades of struggle, including many failed attempts by the U.S. over the years to align itself with other developed and developing nations in subscribing to the world\u27s oldest and most extensive treaty protecting the rights of authors. The step was at last achieved in the closing hours of the hectic session of the Congress shortly before the Presidential election. It was achieved, also, in the face of internal political maneuvering that threatened the adherence bills with delay and possible defeat until the last moment