<i>SOX9</i> chromatin folding domains correlate with its real and putative distant <i>cis</i>-regulatory elements

作     者：Smyk, Marta Akdemir, Kadir Caner Stankiewicz, Pawel 

作者机构：Inst Mother & Child Hlth Dept Med Genet Warsaw Poland Univ Texas MD Anderson Canc Ctr Genom Med Dept Houston TX 77030 USA Baylor Coll Med Dept Mol & Human Genet One Baylor PlazaRm R809 Houston TX 77030 USA 

出 版 物：《NUCLEUS》 (细胞核)

年 卷 期：2017年第8卷第2期

页      面：182-187页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 071009[理学-细胞生物学] 09[农学] 0901[农学-作物学] 090102[农学-作物遗传育种] 

主　　题：chromatin looping long distance gene regulation non-coding variants structural variants tissue-specific enhancers 

摘      要：Evolutionary conserved transcription factor SOX9, encoded by the dosage sensitive SOX9 gene on chromosome 17q24.3, plays an important role in development of multiple organs, including bones and testes. Heterozygous point mutations and genomic copy-number variant (CNV) deletions involving SOX9 have been reported in patients with campomelic dysplasia (CD), a skeletal malformation syndrome often associated with male-to-female sex reversal. Balanced and unbalanced structural genomic variants with breakpoints mapping up to 1.3 Mb up- and downstream to SOX9 have been described in patients with milder phenotypes, including acampomelic campomelic dysplasia, sex reversal, and Pierre Robin sequence. Based on the localization of breakpoints of genomic rearrangements causing different phenotypes, 5 genomic intervals mapping upstream to SOX9 have been defined. We have analyzed the publically available database of high-throughput chromosome conformation capture (Hi-C) in multiple cell lines in the genomic regions flanking SOX9. Consistent with the literature data, chromatin domain boundaries in the SOX9 locus exhibit conservation across species and remain largely constant across multiple cell types. Interestingly, we have found that chromatin folding domains in the SOX9 locus associate with the genomic intervals harboring real and putative regulatory elements of SOX9, implicating that variation in intra-domain interactions may be critical for dynamic regulation of SOX9 expression in a cell type-specific fashion. We propose that tissue-specific enhancers for other transcription factor genes may similarly utilize chromatin folding sub-domains in gene regulation.