Long noncoding RNA HOTTIP cooperates with CCCTC-binding factor to coordinate HOXA gene expression

Feng Wang; Zhongqiong Tang; Honglian Shao; Jun Guo; Tao Tan; Yang Dong; Lianbing Lin

doi:10.1016/j.bbrc.2018.04.173

Long noncoding RNA HOTTIP cooperates with CCCTC-binding factor to coordinate HOXA gene expression

Biochem Biophys Res Commun. 2018 Jun 12;500(4):852-859. doi: 10.1016/j.bbrc.2018.04.173. Epub 2018 May 1.

Authors

Feng Wang¹, Zhongqiong Tang¹, Honglian Shao², Jun Guo¹, Tao Tan³, Yang Dong⁴, Lianbing Lin⁵

Affiliations

¹ Faculty of Life Science and Technology, Kunming University of Science and Technology, 727 South Jingming Road, Chenggong District, Kunming, Yunnan Province, 650500, China.
² Faculty of Life Science and Technology, Kunming University of Science and Technology, 727 South Jingming Road, Chenggong District, Kunming, Yunnan Province, 650500, China; Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, No. 1 Boda Road, Yuhua Area, Chenggong District, Kunming, Yunnan, 650500, China.
³ Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, No. 1 Boda Road, Yuhua Area, Chenggong District, Kunming, Yunnan, 650500, China.
⁴ College of Biological Big Data, Yunan Agricultural University, 452 Fengyuan Road, Kunming, Yunnan Province, 650201, China.
⁵ Faculty of Life Science and Technology, Kunming University of Science and Technology, 727 South Jingming Road, Chenggong District, Kunming, Yunnan Province, 650500, China. Electronic address: [email protected].

PMID: 29698677
DOI: 10.1016/j.bbrc.2018.04.173

Abstract

The spatiotemporal control of HOX gene expression is dependent on positional identity and often correlated to their genomic location within each loci. Maintenance of HOX expression patterns is under complex transcriptional and epigenetic regulation, which is not well understood. Here we demonstrate that HOTTIP, a lincRNA transcribed from the 5' edge of the HOXA locus, physically associates with the CCCTC-binding factor (CTCF) that serves as an insulator by organizing HOXA cluster into disjoint domains, to cooperatively maintain the chromatin modifications of HOXA genes and thus coordinate the transcriptional activation of distal HOXA genes in human foreskin fibroblasts. Our results reveal the functional connection of HOTTIP and CTCF, and shed light on lincRNAs in gene activation and CTCF mediated chromatin organization.

Keywords: Chromatin boundary; HOX genes; Positional identity; Transcriptional regulation; ncRNAs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
CCCTC-Binding Factor / genetics*
CCCTC-Binding Factor / metabolism
Cell Line
Chromatin / chemistry
Chromatin / metabolism
Epigenesis, Genetic*
Fibroblasts / cytology
Fibroblasts / metabolism
Foreskin / cytology
Foreskin / metabolism
Histones / genetics*
Histones / metabolism
Homeodomain Proteins / genetics*
Homeodomain Proteins / metabolism
Humans
Male
Protein Binding
Protein Isoforms / genetics
Protein Isoforms / metabolism
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism
Transcription Factors / genetics*
Transcription Factors / metabolism
Transcription, Genetic

Substances

CCCTC-Binding Factor
CTCF protein, human
Chromatin
Histones
Homeodomain Proteins
Protein Isoforms
RNA, Long Noncoding
Transcription Factors
homeobox A1 protein
long noncoding RNA HOTTIP, human