TY  - JOUR
A1  - Szafranski, Przemyslaw
A1  - Dharmadhikari, Avinash V.
A1  - Brosens, Erwin
A1  - Gurha, Priyatansh
A1  - Kołodziejska, Katarzyna E.
A1  - Zhishuo, Ou
A1  - Dittwald, Piotr
A1  - Majewski, Tadeusz
A1  - Mohan, K. Naga
A1  - Chen, Bo
A1  - Person, Richard E.
A1  - Tibboel, Dick
A1  - de Klein, Annelies
A1  - Pinner, Jason
A1  - Chopra, Maya
A1  - Malcolm, Girvan
A1  - Peters, Gregory
A1  - Arbuckle, Susan
A1  - Guiang, Sixto F.
A1  - Hustead, Virginia A.
A1  - Jessurun, Jose
A1  - Hirsch, Russel
A1  - Witte, David P.
A1  - Maystadt, Isabelle
A1  - Sebire, Neil
A1  - Fisher, Richard
A1  - Langston, Claire
A1  - Sen, Partha
A1  - Stankiewicz, Paweł
T1  - Small noncoding differentially methylated copy-number variants, including lncRNA genes, cause a lethal lung developmental disorder
Y1  - 2013/01/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 23 
EP  - 33 
DO  - 10.1101/gr.141887.112 
VL  - 23 
IS  - 1 
UR  - http://genome.cshlp.org/content/23/1/23.abstract 
N2  - An unanticipated and tremendous amount of the noncoding sequence of the human genome is transcribed. Long noncoding RNAs (lncRNAs) constitute a significant fraction of non-protein-coding transcripts; however, their functions remain enigmatic. We demonstrate that deletions of a small noncoding differentially methylated region at 16q24.1, including lncRNA genes, cause a lethal lung developmental disorder, alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), with parent-of-origin effects. We identify overlapping deletions 250 kb upstream of FOXF1 in nine patients with ACD/MPV that arose de novo specifically on the maternally inherited chromosome and delete lung-specific lncRNA genes. These deletions define a distant cis-regulatory region that harbors, besides lncRNA genes, also a differentially methylated CpG island, binds GLI2 depending on the methylation status of this CpG island, and physically interacts with and up-regulates the FOXF1 promoter. We suggest that lung-transcribed 16q24.1 lncRNAs may contribute to long-range regulation of FOXF1 by GLI2 and other transcription factors. Perturbation of lncRNA-mediated chromatin interactions may, in general, be responsible for position effect phenomena and potentially cause many disorders of human development. 
ER  -