Format

Send to

Choose Destination
Neuron. 2019 Nov 6;104(3):512-528.e11. doi: 10.1016/j.neuron.2019.08.002. Epub 2019 Sep 4.

Nucleome Dynamics during Retinal Development.

Author information

1
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
2
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
3
Cytogenetics Shared Resource, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
4
Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
5
Cellular Imaging Shared Resource, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
6
Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
7
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: xiang.chen@stjude.org.
8
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN 38163, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: michael.dyer@stjude.org.

Abstract

More than 8,000 genes are turned on or off as progenitor cells produce the 7 classes of retinal cell types during development. Thousands of enhancers are also active in the developing retinae, many having features of cell- and developmental stage-specific activity. We studied dynamic changes in the 3D chromatin landscape important for precisely orchestrated changes in gene expression during retinal development by ultra-deep in situ Hi-C analysis on murine retinae. We identified developmental-stage-specific changes in chromatin compartments and enhancer-promoter interactions. We developed a machine learning-based algorithm to map euchromatin and heterochromatin domains genome-wide and overlaid it with chromatin compartments identified by Hi-C. Single-cell ATAC-seq and RNA-seq were integrated with our Hi-C and previous ChIP-seq data to identify cell- and developmental-stage-specific super-enhancers (SEs). We identified a bipolar neuron-specific core regulatory circuit SE upstream of Vsx2, whose deletion in mice led to the loss of bipolar neurons.

KEYWORDS:

Hi-C; Vsx2; bipolar neuron; core regulatory circuit; euchromatin; heterochromatin; machine learning; nucleome; retina; super-enhancer

PMID:
31493975
PMCID:
PMC6842117
[Available on 2020-11-06]
DOI:
10.1016/j.neuron.2019.08.002

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center