Chromatin architecture influences transcription by modulating the physical access of regulatory factors to DNA, playing fundamental roles in cell identity. Studies on dopaminergic differentiation have identified coding genes, but the relationship with non-coding genes or chromatin accessibility remains elusive. Using RNA-Seq and ATAC-Seq we profiled differentially expressed transcripts and open chromatin regions during early dopaminergic neuron differentiation. Hierarchical clustering of differentially expressed genes, resulted in 6 groups with unique characteristics. Surprisingly, the abundance of long non-coding RNAs (lncRNAs) was high in the most downregulated transcripts, and depicted positive correlations with target mRNAs. We observed that open chromatin regions decrease upon differentiation. Enrichment analyses of accessibility depict an association between open chromatin regions and specific functional pathways and gene-sets. A bioinformatic search for motifs allowed us to identify transcription factors and structural nuclear proteins that potentially regulate dopaminergic differentiation. Interestingly, we also found changes in protein and mRNA abundance of the CCCTC-binding factor, CTCF, which participates in genome organization and gene expression. Furthermore, assays demonstrated co-localization of CTCF with Polycomb-repressed chromatin marked by H3K27me3 in pluripotent cells, progressively decreasing in neural precursor cells and differentiated neurons. Our work provides a unique resource of transcription factors and regulatory elements, potentially involved in the acquisition of human dopaminergic neuron cell identity.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379280PMC
http://dx.doi.org/10.1038/s41598-021-96263-1DOI Listing

Publication Analysis

Top Keywords

open chromatin
12
chromatin regions
12
chromatin accessibility
8
cell identity
8
dopaminergic differentiation
8
differentially expressed
8
dopaminergic neuron
8
transcription factors
8
chromatin
7
differentiation
5

Similar Publications

A sparse and wide neural network model for DNA sequences.

Neural Netw

December 2024

Norwegian University of Science and Technology, Trondheim, Norway; Jinhua Institute of Zhejiang University, Hangzhou, China.

Accurate modeling of DNA sequences requires capturing distant semantic relationships between the nucleotide acid bases. Most existing deep neural network models face two challenges: (1) they are limited to short DNA fragments and cannot capture long-range interactions, and (2) they require many supervised labels, which is often expensive in practice. We propose a new neural network model called SwanDNA to address the above challenges.

View Article and Find Full Text PDF

Rethinking chromatin accessibility: from compaction to dynamic interactions.

Curr Opin Genet Dev

December 2024

Università Vita-Salute San Raffaele, Via Olgettina 58, 20132 Milan, Italy; IRCCS Ospedale San Raffaele, Experimental Imaging Center, Via Olgettina 58, 20132 Milan, Italy. Electronic address:

The genome is traditionally divided into condensed heterochromatin and open euchromatin. However, recent findings challenge this binary classification and the notion that chromatin condensation solely governs the accessibility of transcription factors (TFs) and, consequently, gene expression. Instead, chromatin accessibility is emerging as a factor-specific property that is influenced by multiple determinants.

View Article and Find Full Text PDF

Targeting Epigenetic Dysregulations in Head and Neck Squamous Cell Carcinoma.

J Dent Res

December 2024

Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.

Head and neck squamous cell carcinoma (HNSCC) is one of the deadliest human cancers, with the overall 5-year survival rate stagnating in recent decades due to the lack of innovative treatment approaches. Apart from the recently Food and Drug Administration-approved epidermal growth factor receptor inhibitor and immune checkpoint inhibitor, alternative therapeutic strategies that target epigenetic abnormalities, an emerging cancer hallmark, remain to be fully explored. A pathological epigenetic landscape, characterized by widespread reprogramming of chromatin modifications such as DNA methylation and histone modifications, which drives transcription deregulation and genome reorganization, has been extensively documented in numerous cancers, including HNSCC.

View Article and Find Full Text PDF

Open chromatin regions (OCRs) play a crucial role in transcriptional regulation and gene expression. In recent years, there has been a growing interest in using plasma cell-free DNA (cfDNA) sequencing data to detect OCRs. By analyzing the characteristics of cfDNA fragments and their sequencing coverage, researchers can differentiate OCRs from non-OCRs.

View Article and Find Full Text PDF

Binding of MAP3773c Protein of subsp. in the Mouse Ferroportin1 Coding Region.

Int J Mol Sci

November 2024

Facultad de Ciencias Químicas e Ingeniería, Universidad Autónoma de Baja California, Tijuana 22390, Mexico.

subsp. (MAP) is known to cause paratuberculosis. One notable protein, MAP3773c, plays a critical role in iron metabolism as a transcription factor.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!