A 42 kb region on human chromosome 9p21 encodes for three distinct tumor suppressors, p16INK4A, p14ARF and p15INK4B, and is altered in an estimated 30–40% of human tumors. The expression of the INK4A-ARF-INK4B gene cluster is silenced by polycomb during normal cell growth and is activated by oncogenic insults and during aging. How the polycomb is recruited to repress this gene cluster is unclear. Here, we show that expression of oncogenic Ras, which stimulates the expression of p15INK4B and p16INK4A, but not p14ARF, inhibits the expression of ANRIL (antisense non-coding RNA in the INK4 locus), a 3.8 kb-long non-coding RNA expressed in the opposite direction from INK4A-ARF-INK4B. We show that the p15INK4B locus is bound by SUZ12, a component of polycomb repression complex 2 (PRC2), and is H3K27-trimethylated. Notably, depletion of ANRIL disrupts the SUZ12 binding to the p15INK4B locus, increases the expression of p15INK4B, but not p16INK4A or p14ARF, and inhibits cellular proliferation. Finally, RNA immunoprecipitation demonstrates that ANRIL binds to SUZ12 in vivo. Collectively, these results suggest a model in which ANRIL binds to and recruits PRC2 to repress the expression of p15INK4B locus.

The chromodomain helicase DNA-binding (CHD) family of enzymes is thought to regulate gene expression, but their role in the regulation of specific genes has been unclear. Here we show that CHD8 is expressed at a high level during early embryogenesis and prevents apoptosis mediated by the tumour suppressor protein p53. CHD8 was found to bind to p53 and to suppress its transactivation activity. CHD8 promoted the association of p53 and histone H1, forming a trimeric complex on chromatin that was required for inhibition of p53-dependent transactivation and apoptosis. Depletion of CHD8 or histone H1 resulted in p53 activation and apoptosis. Furthermore, Chd8−/− mice died early during embryogenesis, manifesting widespread apoptosis, whereas deletion of p53 ameliorated this developmental arrest. These observations reveal a mode of p53 regulation mediated by CHD8, which may set a threshold for induction of apoptosis during early embryogenesis by counteracting p53 function through recruitment of histone H1.

HIV-1 expresses several accessory proteins to counteract host anti-viral restriction factors to facilitate viral replication and disease progression. One such protein, Vpr, has been implicated in affecting multiple cellular processes, but its mechanism remains elusive. Here we report that Vpr targets TET2 for polyubiquitylation by the VprBP-DDB1-CUL4-ROC1 E3 ligase and subsequent degradation. Genetic inactivation or Vpr-mediated degradation of TET2 enhances HIV-1 replication and substantially sustains expression of the pro-inflammatory cytokine interleukin-6 (IL-6). This process correlates with reduced recruitment of histone deacetylase 1 and 2 to the IL-6 promoter, thus enhancing its histone H3 acetylation level during resolution phase. Blocking IL-6 signaling reduced the ability of Vpr to enhance HIV-1 replication. We conclude that HIV-1 Vpr degrades TET2 to sustain IL-6 expression to enhance viral replication and disease progression. These results suggest that disrupting the Vpr-TET2-IL6 axis may prove clinically beneficial to reduce both viral replication and inflammation during HIV-1 infection.

A distinctive magnetic structure in which azimuthal and latitudinal angles of field vectors axe closely related to each other has been found in the interplanetary magnetic field data obtained by Sakigake at 0.8-1.0 AU. In this structure, termed a "planar magnetic structure" (PMS), the magnetic field vectors are nearly parallel to a fixed plane. This plane includes the spiral direction but is inclined to the ecliptic plane from 30 ø to 85 ø . The field vectors take almost all directions parallel to this plane. The PMS consists of several segments in which field directions are almost constant, and the segments axe separated by tangential discontinuities where directional changes of the field vector occur abruptly without showing any preferred polaxization. The ion number density, the ion temperature, and the plasma/3 tend to be higher in the PMS than in the surrounding plasma. The PMS events are cleaxly distinct from "magnetic clouds" both in the field configuration and in the plasma conditions. During the 25-month period from July 1985 to July 1987, eight PMS events with durations of several hours have been identified. The PMS events may be associated with newly emerging magnetic structure in the photosphere from which magnetic tongues are extended into interplanetaxy space. 1. netic field quite well [e.g., Behannon, 1978]. According to this model, the lines of force of the interplanetary magnetic field are parallel to an Archimedean spiral, and the north-south component of the field Bz is zero. While Parker's model can represent the average magnetic field of the solar wind, high time resolution data of the interplanetary magnetic field do not always agree with the model. Sometimes deviations of the field direction from the Archimedean spiral direction are as large as 90 ø , and the magnetic field vectors are almost perpendicular to the ecliptic plane. This raises a question about the causes of the deviation of the interplanetary magnetic field from the Archimedean spiral. Compression of the solar wind plasma associated with the steepening of high-speed streams [Rosenberg and Coleman, 1980] and draping of the field lines around a fast-moving plasmoid [Gosling and McComas, 1987; McComas et al., 1988] can generate directional changes of the magnetic field. However, nonspiral magnetic fields are not always associated with fast streams. Nonspiral fields which are not associated with fast streams can be due to transverse waves propagating in the interplanetary magnetic field. Alfv•n waves, which are often observed in interplanetary space, cause directional changes in the magnetic field [e.g., Belcher and Davis, 1971]. However, the deviations in the interplanetary magnetic field directions caused by Alfv•n waves would be limited to a finite angular range which is less than 90 ø with respect to the spiral direction even when the amplitude of the Alfv•n wave is large. Another candidate which can cause significant deviations from the spiral field observed in interplanetary space is the so-called "magnetic cloud" emitted fr...