Stability of XIST repression in relation to genomic imprinting following global genome demethylation in a human cell line

DNA methylation is essential in X chromosome inactivation and genomic imprinting, maintaining repression of XIST in the active X chromosome and monoallelic repression of imprinted genes. Disruption of the DNA methyltransferase genes DNMT1 and DNMT3B in the HCT116 cell line (DKO cells) leads to global DNA hypomethylation and biallelic expression of the imprinted gene IGF2 but does not lead to reactivation of XIST expression, suggesting that XIST repression is due to a more stable epigenetic mark than imprinting. To test this hypothesis, we induced acute hypomethylation in HCT116 cells by 5-aza-2′-deoxycytidine (5-aza-CdR) treatment (HCT116-5-aza-CdR) and compared that to DKO cells, evaluating DNA methylation by microarray and monitoring the expression of XIST and imprinted genes IGF2, H19, and PEG10. Whereas imprinted genes showed biallelic expression in HCT116-5-aza-CdR and DKO cells, the XIST locus was hypomethylated and weakly expressed only under acute hypomethylation conditions, indicating the importance of XIST repression in the active X to cell survival. Given that DNMT3A is the only active DNMT in DKO cells, it may be responsible for ensuring the repression of XIST in those cells. Taken together, our data suggest that XIST repression is more tightly controlled than genomic imprinting and, at least in part, is due to DNMT3A.

Stability of XIST repression in relation to genomic imprinting following global genome demethylation in a human cell line.

DNA methylation is essential in X chromosome inactivation and genomic imprinting, maintaining repression of XIST in the active X chromosome and monoallelic repression of imprinted genes. Disruption of the DNA methyltransferase genes DNMT1 and DNMT3B in the HCT116 cell line (DKO cells) leads to global DNA hypomethylation and biallelic expression of the imprinted gene IGF2 but does not lead to reactivation of XIST expression, suggesting that XIST repression is due to a more stable epigenetic mark than imprinting. To test this hypothesis, we induced acute hypomethylation in HCT116 cells by 5-aza-2'-deoxycytidine (5-aza-CdR) treatment (HCT116-5-aza-CdR) and compared that to DKO cells, evaluating DNA methylation by microarray and monitoring the expression of XIST and imprinted genes IGF2, H19, and PEG10. Whereas imprinted genes showed biallelic expression in HCT116-5-aza-CdR and DKO cells, the XIST locus was hypomethylated and weakly expressed only under acute hypomethylation conditions, indicating the importance of XIST repression in the active X to cell survival. Given that DNMT3A is the only active DNMT in DKO cells, it may be responsible for ensuring the repression of XIST in those cells. Taken together, our data suggest that XIST repression is more tightly controlled than genomic imprinting and, at least in part, is due to DNMT3A.

[Radiological picture of the hand and foot in systemic lupus erythematosus]. / Il quadro radiologico della mano e del piede nel lupus eritematoso sistemico.

A detailed examination of the hands and feet was performed in a group of 34 patients affected by systemic lupus erythematosus (SLE), using low-dose mammographic film and Rank Xerox selenium plate, according to current diagnostic techniques. All patients presented articular symptoms (pain and arthralgia). The high incidence (38,8%) of patients with no radiographic evidence of bone damage-even though articular symptoms are present-is emphasized. In such cases, it is very difficult to distinguish SLE from rheumatoid arthritis, especially as far as therapeutic management and prognosis are concerned. The lack of any "pathognomonic" radiological sign of the lupus arthritis, in the hands as well as in the feet, is then stressed. Nevertheless, arthropathy in SLE is defined as a deforming non-erosive arthritis, with a typical symmetric distribution, affecting most commonly-according to incidence-the proximal interphalangeal and metacarpophalangeal joints. In the hand, arthropathy is referred to as Jaccoud's type arthritis, because it is characterized by joint deformities which can be corrected. In the foot, the main abnormalities include hallux valgus, subluxation of the metatarsophalangeal joints and widening of the forefoot.

[The shoulder in basic calcium phosphate microcrystal deposit disease]. / La spalla nella malattia da depositi microcristallini di fosfato basico di calcio.

Basic calcium phosphate (BCP) crystal deposition can lead to periarticular collections associated with typical radiographic findings, most frequently observed in the shoulder. Moreover, these deposits may be revealed in other articular sites (i.e., wrist, hand, foot, elbow, hip, etc.). Initially, the calcium deposits may appear poorly defined (cloudlike); afterwards, they may reveal different patterns (linear, triangular or circular areas), changing in size, configuration and site. Adjacent bone may be normal, although osteoporosis, cystic lesions and reactive sclerosis are reported. The radiographic appearance of calcifications will depend upon the exact location of the deposits in the specific tendon of the rotator cuff, the adjacent bursae and the soft tissues.

["Cupid's bow" contour of the lumbar vertebrae]. / Il profilo ad "arco di Cupido" delle vertebre lombari.

The cortical margin of the inferior end plate of lumbar vertebral bodies, in the frontal projection, frequently simulates the curvature of a bow, aimed cephalad. On lateral view, the two concavities are superimposed and lie in the posterior portion of the vertebral body. The aspect, called "Cupid's bow" must be considered a normal anatomic variant and should not be confused with diseases affecting the spine. The incidence and degree of the finding are discussed.

[Embolization in bladder hemorrhage of neoplastic origin]. / L'embolizzazione nelle emorragie vescicali di origine neoplastica.

The authors report on their two years experience about hypogastric transarterial embolization in the treatment of urinary bladder intractable neoplastic hemorrhage. They discuss about materials for embolization and treatment of pain for acute ischaemia secondary to embolization.