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Transcription Sin3 and NuRD in transcription regulation


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Transcription Sin3 and NuRD in transcription regulation

Sin3 and NuRD in transcription regulation

Activation and repression of gene expression correlate with the state of acetylationof the histones. In general, histone acetylation correlates with more open chromatin andactive gene expression, whereas deacetylation correlates with closed chromatin andrepressed gene expression. NuRD and Sin3 are two major c lass I histonedeacetylase-containing complexes. These complexes play important roles in distinctaspects of embryonic and post-embryonic development [1], [2].

NuRD and Sin3 both contain Histone deacetylase class I, acomplex that consists of Histone deacetylase 1 and 2 ( Hdac1 and Hdac2), Retinoblastomabinding protein 4 and 7 ( Rbbp4 and Rbbp7). In addition, NuRD may contain bothGATA zinc finger domain containing 2A and 2B ( p66alpha and p66beta ).Metastasis associated 1, 2 and 3 ( MTA1, MTA2 and MTA3 ) aremutually exclusive within NuRD, as are Methyl-CpG binding domain protein 2 and 3( MBD2 or MBD3 ) [1], [2].

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 andSAP130 ) and either SIN3 homolog A ( Sin3a ) or SIN3 homolog B (Sin3b ) [1], [2].

Sin3 complexes have also been shown to interact with a variety ofdevelopmentally important factors that are not directly involved in cell cycle control.For example, Sin3 recruitment is required for repression by RE1-silencingtranscription factor ( NRSF ) [3], [4] that silencesneuronal gene expression programmes in non-neuronal tissues [5] and fetalcardiac genes in adult cardiac myocytes [6], [2].

It has also been proposed that the unliganded nuclear hormone receptors Thyroidhormone receptor alpha ( TR-alpha ), Retinoic acid receptor alpha and beta (RAR-alpha and RAR-beta ), Peroxisome proliferator-activated receptor alpha( PPAR-alpha) [7], [8], [9] and othertranscription factors can repress their targets by recruiting co-repressor supercomplexescontaining Sin3 and closely related co-repressors nuclear receptor co-repressor 1and 2 ( N-CoR and SMRT ), Splicing factor proline/glutamine-rich (PSF ) and Non-POU domain containing octamer-binding ( NRB54 ) [10], [2].