» Articles » PMID: 24503509

TGF-β Signaling to Chromatin: How Smads Regulate Transcription During Self-renewal and Differentiation

Overview
Date 2014 Feb 8
PMID 24503509
Citations 91
Authors
Affiliations
Soon will be listed here.
Abstract

Ligands of the TGF-β superfamily (including the TGF-βs, Nodal and BMPs) play instructive roles during embryonic development. This is achieved by regulation of genes important for both maintaining pluripotency and germ layer specification and differentiation. Here we review how the TGF-β superfamily ligands signal to the chromatin to regulate transcription during development. The effectors of the pathway, the Smad transcription factors, are regulated in a combinatorial and spatiotemporal manner. This occurs via post-translational modifications affecting stability, localization and activity, as well as through interactions with other transcription factors and chromatin modifying enzymes, which occur on DNA. Expression profiling and Chromatin Immunoprecipitation have defined Smad target genes and binding sites on a genome-wide scale, which vary between cell types and differentiation stages. This has led to the insight that Smad-mediated transcriptional responses are influenced by the presence of master transcription factors, such as OCT4, SOX2 and NANOG in embryonic stem cells, interaction with other signal-induced factors, as well as by the general chromatin remodeling machinery. Interplay with transcriptional repressors and the polycomb group proteins also regulates the balance between expression of self-renewal and mesendoderm-specific genes in embryonic stem cells and during early development.

Citing Articles

Mechanistic studies of chondroitin sulfate/dermatan sulfate isolated from freshwater fish discards on osteogenesis in MC3T3-E1 cells.

Gavva C, Sharan K, Chilkunda N Glycoconj J. 2025; 42(1):15-26.

PMID: 39883365 DOI: 10.1007/s10719-025-10178-x.


Expression Patterns of , , and Reveal Insights into Heterosis for Growth of Hybrid Offspring between and .

Du X, Zhao Y, Li J, Xie W, Lyu L, Chen S Genes (Basel). 2024; 15(7).

PMID: 39062724 PMC: 11276220. DOI: 10.3390/genes15070945.


State-of-the-Art Differentiation Protocols for Patient-Derived Cardiac Pacemaker Cells.

Torre E, Mangoni M, Lacampagne A, Meli A, Mesirca P Int J Mol Sci. 2024; 25(6).

PMID: 38542361 PMC: 10970580. DOI: 10.3390/ijms25063387.


Bone morphogenetic protein signaling: the pathway and its regulation.

Akiyama T, Raftery L, Wharton K Genetics. 2023; 226(2).

PMID: 38124338 PMC: 10847725. DOI: 10.1093/genetics/iyad200.


BMP signaling in cancer stemness and differentiation.

Zhou W, Yan K, Xi Q Cell Regen. 2023; 12(1):37.

PMID: 38049682 PMC: 10695912. DOI: 10.1186/s13619-023-00181-8.