Sin3 and NuRD in transcription regulation
Activation and repression of gene expression correlate with the state of acetylation
of the histones. In general, histone acetylation correlates with more open chromatin and
active gene expression, whereas deacetylation correlates with closed chromatin and
repressed gene expression. NuRD and
Sin3 are two major class I histone deacetylase-containing
complexes. These complexes play important roles in distinct aspects of embryonic and
post-embryonic development , .
NuRD and Sin3 both contain
Histone deacetylase class I, a complex that consists of
Histone deacetylase 1 and 2 (Hdac1 and Hdac2), Retinoblastoma binding protein 4 and 7
(Rbbp4 and Rbbp7). In addition, NuRD may contain both GATA
zinc finger domain containing 2A and 2B (p66alpha and
p66beta). Metastasis associated 1, 2 and 3
(MTA1, MTA2 and
MTA3) are mutually exclusive within
NuRD, as are Methyl-CpG binding domain protein 2 and 3
(MBD2 or MBD3) , .
Sin3 complexes contain Suppressor of defective silencing
3 homolog (SDS3), AT rich interactive domain 4A and 4B
(ARID4A and ARID4B),
Sin3A-associated protein 18kDa, 30kDa and 130kDa (SAP18,
SAP30 and SAP130) and either
SIN3 homolog A (Sin3a) or SIN3 homolog B
(Sin3b) , .
Sin3 complexes have also been shown to interact with a
variety of developmentally important factors that are not directly involved in cell cycle
control. For example, Sin3 recruitment is required for
repression by RE1-silencing transcription factor (NRSF)
,  that silences neuronal gene expression programmes in
non-neuronal tissues  and fetal cardiac genes in adult cardiac myocytes
It has also been proposed that the unliganded nuclear hormone receptors Thyroid
hormone receptor alpha (TR-alpha), Retinoic acid receptor
alpha and beta (RAR-alpha and
RAR-beta), Peroxisome proliferator-activated receptor alpha
(PPAR-alpha) , ,  and other transcription
factors can repress their targets by recruiting co-repressor supercomplexes containing
Sin3 and closely related co-repressors nuclear receptor
co-repressor 1 and 2 (N-CoR and
SMRT), Splicing factor proline/glutamine-rich
(PSF) and Non-POU domain containing octamer-binding
(NRB54) , .
- Ahringer J
NuRD and SIN3 histone deacetylase complexes in development.
Trends in genetics : TIG 2000 Aug;16(8):351-6
- McDonel P, Costello I, Hendrich B
Keeping things quiet: roles of NuRD and Sin3 co-repressor complexes during mammalian development.
The international journal of biochemistry & cell biology 2009 Jan;41(1):108-16
- Grimes JA, Nielsen SJ, Battaglioli E, Miska EA, Speh JC, Berry DL, Atouf F, Holdener BC, Mandel G, Kouzarides T
The co-repressor mSin3A is a functional component of the REST-CoREST repressor complex.
The Journal of biological chemistry 2000 Mar 31;275(13):9461-7
- Nomura M, Uda-Tochio H, Murai K, Mori N, Nishimura Y
The neural repressor NRSF/REST binds the PAH1 domain of the Sin3 corepressor by using its distinct short hydrophobic helix.
Journal of molecular biology 2005 Dec 9;354(4):903-15
- Schoenherr CJ, Anderson DJ
The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes.
Science (New York, N.Y.) 1995 Mar 3;267(5202):1360-3
- Bingham AJ, Ooi L, Kozera L, White E, Wood IC
The repressor element 1-silencing transcription factor regulates heart-specific gene expression using multiple chromatin-modifying complexes.
Molecular and cellular biology 2007 Jun;27(11):4082-92
- Heinzel T, Lavinsky RM, Mullen TM, Soderstrom M, Laherty CD, Torchia J, Yang WM, Brard G, Ngo SD, Davie JR, Seto E, Eisenman RN, Rose DW, Glass CK, Rosenfeld MG
A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression.
Nature 1997 May 1;387(6628):43-8
- Xu HE, Stanley TB, Montana VG, Lambert MH, Shearer BG, Cobb JE, McKee DD, Galardi CM, Plunket KD, Nolte RT, Parks DJ, Moore JT, Kliewer SA, Willson TM, Stimmel JB
Structural basis for antagonist-mediated recruitment of nuclear co-repressors by PPARalpha.
Nature 2002 Feb 14;415(6873):813-7
- Pile LA, Spellman PT, Katzenberger RJ, Wassarman DA
The SIN3 deacetylase complex represses genes encoding mitochondrial proteins: implications for the regulation of energy metabolism.
The Journal of biological chemistry 2003 Sep 26;278(39):37840-8
- Mathur M, Tucker PW, Samuels HH
PSF is a novel corepressor that mediates its effect through Sin3A and the DNA binding domain of nuclear hormone receptors.
Molecular and cellular biology 2001 Apr;21(7):2298-311