Faculty Collaboration Database

Coordinate expression of regulatory genes differentiates embryonic and perinatal forms of biliary atresia. Hepatology 2004 Apr;39(4):954-62

Date

04/02/2004

Pubmed ID

15057899

DOI

10.1002/hep.20135

Scopus ID

2-s2.0-1842480207 (requires institutional sign-in at Scopus site)   74 Citations

Abstract

The molecular basis for the embryonic and perinatal clinical forms of biliary atresia is largely undefined. In this study, we aimed to: 1) determine if the clinical forms can be differentiated at the transcriptional level, and 2) search for molecular mechanisms underlying phenotypic differences. To this end, we generated biotinylated cRNA probes from livers of age-matched infants with the embryonic (n = 5) and perinatal (n = 6) forms of biliary atresia at the time of diagnosis and hybridized them against the Affymetrix human HG-U133 A and B microarrays containing 44,760 gene products. Data filtering and two-way cluster analysis of the gene expression platform identified 230 genes with an expression profile that is highly distinctive of the clinical phenotypes. Functionally, the profile did not reveal a higher-order function for a specific cell type; instead, it uncovered a coordinated expression of regulatory genes. These regulatory genes were predominantly represented in the embryonic form (45% of genes), with a unique pattern of expression of genes involved in chromatin integrity/function (Smarca-1, Rybp, and Hdac3) and the uniform overexpression of five imprinted genes (Igf2, Peg3, Peg10, Meg3, and IPW), implying a failure to downregulate embryonic gene programs. In conclusion, embryonic and perinatal forms of biliary atresia are distinguished by gene expression profiling. The coordinate expression of regulators of chromatin structure/function and of imprinted genes provides evidence for a transcriptional basis for the pathogenesis of the embryonic form of biliary atresia. Further studies exploring these biological processes are required to determine the significance of these findings.

Author List

Zhang DY, Sabla G, Shivakumar P, Tiao G, Sokol RJ, Mack C, Shneider BL, Aronow B, Bezerra JA

Author

Cara Lynn Mack MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Biliary Atresia
Biopsy
Cell Cycle Proteins
Cytokines
Female
Gene Expression Regulation, Developmental
Genomic Imprinting
Humans
Infant
Infant, Newborn
Male
Oligonucleotide Array Sequence Analysis
Phenotype