Narrowing the FOXF1 distant enhancer region on 16q24.1 critical for ACDMPV.

Abstract

BACKGROUND:

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal lung developmental disorder caused by heterozygous point mutations or genomic deletions involving FOXF1 or its 60-kb tissue-specific enhancer region mapping 270 kb upstream of FOXF1 and involving fetal lung-expressed long non-coding RNA genes and CpG-enriched sites. Recently, we have proposed that the FOXF1 locus at 16q24.1 may be a subject of genomic imprinting.

FINDINGS:

Using custom-designed aCGH and Sanger sequencing, we have identified a novel de novo 104 kb genomic deletion upstream of FOXF1 in a patient with histopathologically verified full phenotype of ACDMPV. This deletion allowed us to further narrow the FOXF1 enhancer region and identify its critical 15-kb core interval, essential for lung development. This interval harbors binding sites for lung-expressed transcription factors, including GATA3, ESR1, and YY1, and is flanked by the lncRNA genes and CpG islands. Bisulfite sequencing of one of these CpG islands on the non-deleted allele showed that it is predominantly methylated on the maternal chromosome 16.

CONCLUSIONS:

Substantial narrowing and bisulfite sequencing of the FOXF1 enhancer region on 16q24.1 provided new insights into its regulatory function and genomic imprinting.

• Authors: Przemyslaw Szafranski, Carmen Herrera, Lori A Proe, Brittany Coffman, Debra L Kearney, Edwina Popek, Paweł Stankiewicz
• Journal: Clinical epigenetics (Clin Epigenetics) Vol. 8 Pg. 112 ( 2016) ISSN: 1868-7083 [Electronic] Germany
• PMID: 27822317 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• ESR1 protein, human
• Estrogen Receptor alpha
• FOXF1 protein, human
• Forkhead Transcription Factors
• GATA3 Transcription Factor
• GATA3 protein, human
• RNA, Long Noncoding
• YY1 Transcription Factor
• YY1 protein, human

Topics

• Binding Sites
• Chromosomes, Human, Pair 16 (genetics)
• Comparative Genomic Hybridization
• CpG Islands
• Enhancer Elements, Genetic
• Estrogen Receptor alpha (genetics)
• Female
• Forkhead Transcription Factors (chemistry, genetics)
• GATA3 Transcription Factor (genetics)
• Genomic Imprinting
• Humans
• Infant, Newborn
• Male
• Persistent Fetal Circulation Syndrome (genetics)
• RNA, Long Noncoding (genetics)
• Sequence Analysis, DNA (methods)
• Sequence Deletion
• YY1 Transcription Factor (genetics)