As cells differentiate during embryogenesis and during differentiation from stem cells in adult organisms, many of the genes induced during the process are initially in repressed regions of heterochromatin in undifferentiated progenitor cells. Activation of these genes requires that the chromatin environment of their transcription-control regions become decondensed so that transcription factors can bind to enhancers and promoter proximal control elements and so that the general transcription factors and Pol II can bind to promoters. In many cases, this decondensation is initiated by special pioneer transcription factors that can bind to their cognate binding sites in DNA even when those sites are within repressed heterochromatic regions of chromatin. These factors have a DNA-binding domain that binds to one side of the DNA helix in a manner similar to the bacteriophage 434 repressor (see Figure 1). This domain allows these factors to bind to their specific binding sites while the DNA is wrapped around a histone octamer with the opposite side of the DNA against the surfaces of histones.

Fig1. Interaction of bacteriophage 434 repressor with DNA. Ribbon diagram of 434 repressor bound to its specific operator DNA. The recognition helices are shown in green. The α helices N-terminal to the recognition helix and the turn in the polypeptide backbone between the helices in the helix-turn-helix structural motif are shown in yellow and red, respectively. The protein interacts intimately with one side of the DNA molecule over a length of 1.5 turns. [Data from A. K. Aggarwal et al., 1988, Science 242:899, PDB ID 2ori.]

One example of pioneer transcription factors initiating the process of transcriptional activation involves the liver-specific gene Alb1, encoding serum albumin, a major constituent of blood serum that is secreted into the blood by hepatocytes. In the developing mouse, the FoxA and GATA-4 or GATA-6 transcription factors are the first transcription factors to bind to an Alb1 enhancer in undifferentiated gut endodermal cells destined to develop into the liver. FoxA has a “winged helix” DNA-binding domain that binds to one side of the DNA helix containing the FoxA-binding site. GATA factors are also able to bind to their specific sites in DNA when those sites are included in nucleosomal DNA wrapped around a histone octamer. The FoxA and GATA-4/6 activation domains may then interact with chromatin remodeling complexes and histone acetylase complexes to decondense the chromatin of the 120-bp Alb1 enhancer, allowing the observed subsequent binding of four additional transcription factors in the nascent liver bud that develops later.

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طاقم أرتميس 2 يحطم رقما قياسيا ويستعرض الجانب البعيد للقمر

"أرتيميس 2" تنطلق حول القمر وتحطم الرقم القياسي

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مواضيع ذات صلة

Regulation of Pre-mRNA Processing

Transcription Initiation by Pol I and Pol III Is Analogous to That by Pol II

The Mediator Complex Forms a Molecular Bridge Between Activation Domains and Pol II

Genetic Material can be Altered & Rearranged

Translation and protein production

Epigenetic Regulation of Transcription

Chromatin-Remodeling Complexes Help Activate or Repress Transcription

Activators Can Direct Histone Acetylation at Specific Genes

Repressors Can Direct Histone Deacetylation at Specific Genes

Formation of Heterochromatin Silences Gene Expression at Telomeres, near Centromeres, and in Other Regions

Multiprotein Complexes Form on Enhancers

Transcription Factor Interactions Increase Gene-Control Options